GI physiology

Question 1

What are the contractile proteins in smooth muscle?

Answer 1

• Actin and myosin
• Actin is thin filaments, myosin is thick filaments
• Ratio is 10:1 thin:thick
○ In skelatal muscle it’s 2:1
• Contraction of smooth muscle cell occurs when myosin interacts with actin, triggered by the entry of Ca ions into the cell
• Formation of a complex of Ca and calmodulin activates myosin light chain kinase which phosphorylates myosin and allows cross-bridge formation to occur

Question 2

Describe the pathway of smooth muscle contraction

Answer 2

• Calcium enters cell either from SR or from outside
  
  • Calcium binds calmodulin
  • Calmodulin binds and activates MLCK - myosin light chain kinase
  • Phosphorylation of myosin occurs
  • Contraction cycle takes place
  • MLCP - myosin light chain phosphatase will remove the phosphate group and inactivate the contraction cycle
  • Eventually calmodulin pops off MLCK and deactivates that enzyme

Question 3

What is BER?

Answer 3

• Basic electrical rhythm
• Property of smooth muscle cells that allows them to approach depolarization potentials but not reach them
• Needs ach to get to threshold, initiate AP and fully initiate contractile cycle
• This is what gives smooth muscle tone and rhythmicity, but still allows for NT control
*also called slow waves

Question 4

Describe the muscular contractions that facilitate peristalsis

Answer 4

• Circular muscle contraction behind the bolus
• Longitudinal muscle contraction ahead of bolus
○ Kinda like a worm
• Contraction of circular muscles propels bolus forward

Question 5

Deglutition = ?

Answer 5

• Deglutition = swallowing
  
  • Represents the aboral movement of a food bolus beyond the upper esophageal sphincter
  • Reflects a combo of both voluntary and involuntary contractile responses
  • Divided into voluntary, pharyngeal and esophageal phases
  • Sensory receptors in the pharynx send information to swallowing center in brain and that coordinates all of the subsequent involuntary events

Question 6

Describe the events that take place in deglutition

Answer 6

• Tongue separates a portion of food and moves it backwards into pharynx
  
  • This pushes soft palate upward, the upper constrictor muscle contracts and these actions together close off the nasopharynx
  • From this point swallowing is a reflex coordinated by autonomic nerves
  • Main function of pharyngeal phase is to direct food to esophagus, not trachea
  • For 1-2 seconds respiration is inhibited centraly, the larynx raises and the glottis closes to prevent bolus from entering trachea
  • Upper esophageal spincter (UES) relaxes and coordinated contraction or peristaltic wave of the middle and lower constrictor muscles propels bolus into esophagus

Question 7

What controls the peristaltic wave in the lower esophagus?

Answer 7

• Remember there must be coordinated contractions
  
  • There must also be a LES relaxation
  • Vagus nerve controls this, receiving information from swallowing center in brainstem
  • Local myenteric complex can maintain swallowing if need be

Question 8

Describe the motions that are happening in the stomach when food hits it

Answer 8

• After eating, contractions start around mid-stomach at the frequency of slow waves
○ 3/min
• Peristaltic waves push a bolus toward the antrum
• The contractions become stronger and faster in antrum, outrunning bolus
• Pyolic openin is small and most content is relfected backward towards body of stomach for mixing and grinding purposes
• Digestive juice mixture is called chyme
• Transient opening of pylorus allows smaller particles and chyme to leave the stomach and enter duodenum

Question 9

What signals need be present to increase gastric emptying?

Answer 9

• Distension. Increased stretch leads to increased peristalsis through vagal and myenteric relfexes and decreases pyloric tone
• Gastrin is a hormone secreted in response to presence of food in stomach
• Gastrin also increased peristaltic contraction and decreases pyloric tone
○ Thus it’s the combo of gastrin and distension that increase gastric emptying

Question 10

What happens when fat reaches the duodenum?

Answer 10

• Release of CCK - cholecystokinin by enteric endocrine cells
  
  • CCK decreases gastric motility providing a further method whereby the actions in the duodenum decrease the rate of gastric emptying to prevent overwhelming of the intestinal absorptive capacity

Question 11

What is the reflex of the GI system when food hits the duodenum?

Answer 11

• Due to distension and irritation (acidity), duodenum signals to decrease gastric peristalsis and increase pyloric tone
  
  • Duodenum controls delivery rate

Question 12

Describe the function of the MMC

Answer 12

• Myoelectric motor complexes
  
  • Housekeeping role.
  • Motilin, hormone produced by small intestine seems to initiate it
  • Sweep down gastric antrum and along small intestines
  • Every 90 min, moves bacteria and indigestible material along down the tube
  • At any one time 40cm of bowel is involved and about 50 peristaltic waves in that section occur in about 10 minutes, then it moves down another 40cm section
  • Eating will inhibit these movements

Question 13

What are hausta?

Answer 13

• Sacculations of the colon

* A result of segmentation contractions, which are designed to mix and remain local

Question 14

When does forward propulsion happen in the colon?

Answer 14

• During mass movement
  
  • Constitute a type of motility not seen elsewhere in the digestive tract
  • AKA giant migrating contractions, very intense and prolonged peristaltic contraction that strips an area of large intestine clear of contents
  • Segmental activity temporarily ceases during this and there is a loss of haustration
  • Thus there are segmental activities and mass movements that characterize the major phases of large bowel motility

Question 15

What do parietal cells do?

Answer 15

• Thes are cells in the stomach
• Secrete hydrochloric acid and a protein called intrinsic factor into the stomach
• Intinsic factor is the only indispensible stomach produced protein
○ This is essential for vitamin B12 absorption
○ People with no stomachs must get B12 injections
• pH of lumen of stomach is 2, so there is a huge E requirement and therefore tons of mitochondria in these cells

Question 16

Why is the pH of venous blood leaving stomach high?

Answer 16

• Bicarbonate ions are secreted out from the parietal cell basolateral side
• HCO3- secretion into blood is called the alkaline tide
○ The purpose for the secretion is to power Cl- movement into parietal cells

Question 17

How is the hydrochloric acid produced by the parietal cells?

Answer 17

• The protons, H+, are produced from the fact that H2O is in equilibrium
• OH is consumed to form HCO3- using CO2 from the blood, and this drives the reaction to produce more H+
• H+ is actively transported across the apical membrane in exchange for K+
○ H/K ATPase
○ Primary active transport
• When H+ is driven out, HCO3- concentration rises as well
• HC)3- is tranported across the basolateral membrane in exchange for Cl- and the downhill movement of HCO3- is used to drive Cl- into cell
○ Cl/HCO3 anion exchanger
○ Secondary active transport
• Cl that accumulates in cells is then transported across the apical membrane by facilitated diffusion
○ Passive transport
• Water then follows the net transport of HCL for osmotic reasons moving from blood to lumen by trans-cellular pathway

Question 18

What three signaling molecules will stimulate an increase in acid secretion from gastric parietal cells?

Answer 18

• NT - ach (parasympathetic)
○ Binds muscarinic receptors on basolateral membrane
○ Leads to activation of a GPCR and rise in Ca
• Hormone - gastrin
○ Likely works by increasing Ca as well
• Paracrine substance - histamine
○ H2 receptors and leads to activation of a different GPCR - adynylate cyclase
○ Adenylate cyclase catalyzes synthesis of cAMP
○ Ca and cAMP activate distinct protein kinases that phosphorylate H/K ATPase
• Histamine and ach sstimulate acid secretion from stimulaton of histamine release from enterochromaffin like cells
○ ECL cells
• Direct pathway - ach, gastrin and histamine direclty stimulate parietal cell and trigger H+ into lumen
• Indirect pathway - ach and gastrin stimulate the ECL cells which secrete histamine

Question 19

What are the direct and indirect ways to stimulate parietal cells to secrete H+ into the lumen?

Answer 19

• Direct pathway - ach, gastrin and histamine direclty stimulate parietal cell and trigger H+ into lumen
  
  • Indirect pathway - ach and gastrin stimulate the ECL cells which secrete histamine

Question 20

What is going on in the cephalic phase of gastric acid secretion?

Answer 20

• Cephalic phase
○ Stimulated by external perception of food being nigh upon us
○ Primarily mediated by vagus nerve
Stimulation of vagus nerve results in release of Ach, triggering of the histamine release from ECL cells, release of gastrin-releasing peptide (GRP) from vagal and enteric neurons and inhibition of somatostatin release from delta cells in stomach (D cells)

Question 21

What does stimulation of the vagus nerve in the cephalic phase of gastric acid secretion do?

Answer 21

• 4 things:
• Stimulation of vagus nerve results in release of Ach,
• triggering of the histamine release from ECL cells,
• release of gastrin-releasing peptide (GRP) from vagal and enteric neurons and
• inhibition of somatostatin release from delta cells in stomach (D cells)

Question 22

What’s going on in between meals with acid secretion?

Answer 22

• Basal (inter-digestive phase)
○ Follows a circadian rhythm
○ Rate of acid secretion is lowest in morning before awakening and highest in evening
○ Resting pH is 3-7
○ Rate is super enhanced by eating. The sight, smell and taste in addition to reflex of swallowing food will initiate the next phase

Question 23

What are the 4 phases of gastric acid secretion?

Answer 23

• Basal (inter-digestive phase)
○ Follows a circadian rhythm
○ Rate of acid secretion is lowest in morning before awakening and highest in evening
○ Resting pH is 3-7
○ Rate is super enhanced by eating. The sight, smell and taste in addition to reflex of swallowing food will initiate the next phase
• Cephalic phase
○ Stimulated by external perception of food being nigh upon us
○ Primarily mediated by vagus nerve
○ Stimulation of vagus nerve results in release of Ach, triggering of the histamine release from ECL cells, release of gastrin-releasing peptide (GRP) from vagal and enteric neurons and inhibition of somatostatin release from delta cells in stomach (D cells)
○ About 30% of gastric secretion in this phase
• Gastric phase
○ Triggered by entry of food into stomach
○ Food distends gastric mucosa, which activates a vagovagal reflex as well as local ENS reflexes
○ Second, partially digested proteins stimulate antral gastrin cells (G cells) to release gastrin
○ 50-60% of total acid secretion in this phase
• Intestinal phase
○ Presence of amino acids and partially digested peptides in proximal small intestine stimulates acid secretion by stimulating duodenal gastrin cells
§ G cells, but duodenal
○ 5-10% of total secretion in this phase

Question 24

Describe the layout of the blood flow to the intestine

Answer 24

• Each intestinal villus recieves an arteriole
• The arteriole divides into capillaries beneath the individual epithelial cells
• Each villus also has a venule and lacteal
• Lacteal is both a lymphatic vessel and the deposit site for lipids that get absorbed
○ Reaches blood stream at thoracic duct
• Venule goes through hepatic portal system

Question 25

Pepsinogen is a zymogen. What activates it?

Answer 25

• The acidic environment of the gastric lumen will turn pepsinogen into pepsin

Question 26

Where does trypsinogen become trypsin?

Answer 26

• In the duodenum, where the enteropeptidase is on the enterocyte surface
  
  • Trypsin can cleave other trypsinogens

Question 27

The major source of carbohydrates in most human diets is what?

Answer 27

• Plant starch = amylopectin

* Polymer of glucos containing both alpha-1,4 and alpha-1,6 linkages

Question 28

Besides starch what is the other common carbohydrate source?

Answer 28

• Sucrose and lactose

* Both disaccharides

Question 29

What is meant by the specificity of amylase?

Answer 29

• Amylase in saliva can only break down alpha-1,4 linkages to produce maltose, maltotriose and alpha-limit dextrin
  
  • It can never produce free glucose

Question 30

Amylose and amylopectin are different how?

Answer 30

• Amylose is a straight chain of polymers

* Amylopectin contains branched chains

Question 31

What does SI activity mean?

Answer 31

• Sucrase-isomaltase
  
  • This is in the mucosa and represents the last stage of small intestinal digestion of branch points of starch to glucose

Question 32

Mucosal maltase-glucoamylase activity does what?

Answer 32

• MGA - mucosal maltase-glucoamylase
  
  • Final step in small intestinal digestion of linear forms of starch to glucose
  • Thus SI and MGA complement each other’s functions

Question 33

What is SGLT1 and what does it do?

Answer 33

• Responsible for trasporting glucose through the apical membrane of enterocytes
  
  • Sodium dependent glucose tansporter
  • Transports glucos and galactose along with Na from the intestinal lumen into cytosol

Question 34

Where is GLUT2?

Answer 34

• Sodium independent fructose transporter

* GLUT2 is on the basolateral side and transports all three monosaccharides from cytosol to the blood

Question 35

What is GLUT5 and what does it do?

Answer 35

• Sodium independent fructose transporter
  
  • Also apical like SGLT1
  • Facilitative glucose transporter example
  • Transports fructos from lumen into cytosol
  • GLUT2 is on the basolateral side and transports all three monosaccharides from cytosol to the blood

Question 36

A patient who has diarrhea upon the ingestion of normal dietary sugars likely has what problem?

Answer 36

• Genetic absence of Na/glucose co-transporter SGLT1
• In the intestinal brush border
• Glucose galactose malabsorption in humans
• Reduced intestinal Na and fluid absorption osmotically
• Also fluid secretion secondary to the osmotic effects of non-absorbed monosaccharide
○ Can treat with replacing dietary glucose with fructose because GLUT5 still works
○ This can be potentially fatal neonatal glucose-galactose malabsorption

Question 37

What are the secreted endopeptidases are called what and what do they do?

Answer 37

• Chew up internal peptide bonds (hydrolyze)
	• Pepsin
		○ Aromatic amino acids
	• Trypsin
		○ Arginine and lysine (R,K)
	• Chymotrypsin
		○ Aromatic amino acids
	• Elastase
		○ Neutral aliphatic amino acids

Question 38

What are the exopeptidases and what do they do?

Answer 38

• Hydrolyze one amino acid at a time from the C terminus towards the N terminus
• Carboxypeptidases A
• Carboxypeptidases B
• Aminopeptidase
○ Clips off one amino acid from N terminus
• Dipeptidyl aminopeptidase
○ Clips off two amino acids from N terminus
• Dipeptidase
○ From dipeptides to amino acids

Question 39

While pepsin, from pepsinogen, is active in the stomach, people with no stomach can still absorb and digest proteins. How?

Answer 39

• The main way that humans absorb and digest proteins is through pancreatic proteases secreted into the small intestine from inactive precursors
○ Trypsinogen
○ Chymotripsinogen
○ Pro-elastase
○ Pro-carboxypeptidase A
○ Pro-carboxypeptidase B
• Steps of small intestine protein digestion:
○ Activation of trypsinogen to trypsin by brush border protease enterokinase
○ Activation of all other precursors by trypsin
○ Trypsin, chymotrypsin, elastase, carboxypeptidase A and B all hydrolyze protein to amino acids and di, tri, and oligopeptides
○ Brush border proteases hydrolyze oligopeptides to amino acids
○ Pancreatic proteases digest themselves and others

Question 40

Describe normal absorption of proteins

Answer 40

• Occurs by sodium dependent co-transport
  
  • Unlike carbohydrate absorption (only monomers) most protein absorption comes through di and tripeptides
  • These get fully chewed to amino acids by cytoplasmic peptidases
  • Amino acids exit the basolateral membrane of the enterocyte by facilitated diffusion and enter blood capillaries

Question 41

What are various disorders of amino acid transport?

Answer 41

• Cysteinuria
○ Lacking Na-dependend amino acid transporter in GI and in kidneys
○ Lose cystein, lysine, arginine and ornithine amino acids in feces and urine
• Hartnup disease
○ Defect or absence of neutral amino acid transporter
• Chronic pancreatitis
○ Trypsin is gone, so all the others appear to be missing as well as trypsin activates all the others

Question 42

Describe the steps involved in triglyceride digestion and absorption:

Answer 42

• Fat droplets are emulsified by bile salts and lecithin to form particles on the order of 1um in diameter
• This process increases the surface area for subsequend digestion by lipase and colipase
○ Colipase = protein that helps to anchor lipase to the surface of the droplets
• The products of lipase digestion are 2’-monoglycerides and fatty acids which are solubilized in bile-salt micelles
• Micelles are cylindrical structures about 10nm across, with hydrophilic groups oriented toward the aqueous phase and hydrophobic groups associating in the interior
• Micelles are required to transport the products of fat digestion through the unstirred water layer near the surface of enterocytes
• The abundance of hydrophilic glycoproteins protruding from the brush border membrane, as well as mucus are responsible for the unstirred layer
• Lipids move in and out of the micelles, and when they strike the cell surface they are able to diffuse passively through the membrane and into the cells
• Inside the enterocytes, triglycerides are re-synthesized from monoglycerides and fatty acids
• They are then packaged into lipoprotein particles called chylomicrons
• In addition to containing triglycerides, chylomicrons contain phospholipids, cholesterol and apolipoproteins
• In the golgi they are incorporated into secrtory vesicles
• Vesicle migrate to the basolateral membrane and the chylomicrons are released into the interstitial space by exocytosis
• They then enter the lacteals because they are too large for capillaries
• Fat soluble vitamins are absobed by precisely the same route as fat digestion products and cholesterol

Question 43

A dietary lipid is what?

Answer 43

• The most abundant storage form of fat in animals and plants = triglyceride
○ Thus the name of dietary lipid
• Harder to absorb and digest than proteins or sugars because of their water insolubility

Question 44

Pancreatic lipase turns triglycerides into what?

Answer 44

• Since triglycerides cannot be efficiently absorbed, they are enzymatically digested
• 2-monoglyceride and two free fatty acids
○ These CAN be absorbed

Question 45

What are the events in triglyceride absorption up to the enterocyte surface?

Answer 45

• Fat droplets are emulsified by bile salts and lecithin to form particles on the order of 1um in diameter
• This process increases the surface area for subsequend digestion by lipase and colipase
○ Colipase = protein that helps to anchor lipase to the surface of the droplets
• The products of lipase digestion are 2’-monoglycerides and fatty acids which are solubilized in bile-salt micelles
• Micelles are cylindrical structures about 10nm across, with hydrophilic groups oriented toward the aqueous phase and hydrophobic groups associating in the interior
• Micelles are required to transport the products of fat digestion through the unstirred water layer near the surface of enterocytes
• The abundance of hydrophilic glycoproteins protruding from the brush border membrane, as well as mucus are responsible for the unstirred layer
• Lipids move in and out of the micelles, and when they strike the cell surface they are able to diffuse passively through the membrane and into the cells

Question 46

What are the steps of triglyceride absorption once they are within the enterocyte?

Answer 46

• Lipids move in and out of the micelles, and when they strike the cell surface they are able to diffuse passively through the membrane and into the cells
  
  • Inside the enterocytes, triglycerides are re-synthesized from monoglycerides and fatty acids
  • They are then packaged into lipoprotein particles called chylomicrons
  • In addition to containing triglycerides, chylomicrons contain phospholipids, cholesterol and apolipoproteins
  • In the golgi they are incorporated into secrtory vesicles
  • Vesicle migrate to the basolateral membrane and the chylomicrons are released into the interstitial space by exocytosis
  • They then enter the lacteals because they are too large for capillaries
  • Fat soluble vitamins are absobed by precisely the same route as fat digestion products and cholesterol

Question 47

What are the fat soluble vitamins and how are they absorbed?

Answer 47

• absorbed the same manner as triglycerides or dietary fat
• • Fat soluble vitamins are absobed by precisely the same route as fat digestion products and cholesterol
• vitamins A, D, E, K

Question 48

What is steatorrhea?

Answer 48

• Excessive loss of fat in the stool
• Hallmark of a diverse group of digestive disorders that cause fat malabsorption
• Also causes fat-soluble vitamin malabsorption
○ Liver disease - bile salts are gone
○ Pancreatic insufficiency - lipase is gone and enzymatic degradation of fat is gone
○ Weight loss medication - these inhibit lipase activity and increase passage of fat from GI tract

Question 49

What are the two most important principles of water reabsorption to note?

Answer 49

• 1 - water readily moves across the intestinal epithelium
○ Thus chyme entering the duodenum is rapidly brouth into isotonic equilibrium with the blood
• 2 - water absorption follows the absoption of solutes and is therefore said to be absorbed isotonically

Question 50

Does water in the GI move from apical to basolateral through specific transport?

Answer 50

• No, it all happens paracellularly

* Water will follow the osmotic gradient

Question 51

In the colon, what is being reabsorbed?

Answer 51

• Water and ions. Water and ions. NOTHING else.
• Na reabsorption from the apical Na channels
○ Epithelial sodium channel or ENaC
• Any rise in plasma aldosterone levels causes very similar changes in colonic epithelia cells of the GI tract to those in the distal nephron of the kidneys
• The colon will absorb more Na and consequently more water
• Another similarity is that more Na absorption means more K secretion across apical membrane
• In the colon there is net K secretion when the lumenal concentration drops below 25mM (I assume this is Na concentration)

Question 52

What are the water soluble vitamins?

Answer 52

• B vitamins
• Vitamin C
• Niacin
• Folic acid
• Pantothenic acid
• Biotin
○ All absorbed by either by co-transport with Na or by passive diffusion
○ Virtually complete in the upper small intestine
○ B12 is the exception which is absorbed in distal ileum with intrinsic factor

Question 53

Diarrhea can result in what electrolyte problems?

Answer 53

• Hypokalemia because of the same mechanism by which extra flow in the kidney can result in hypokalemia
• The K secretion is turned on max because there is such rapid flow that the colon is trying always to raise K levels
○ Think of it like extra flow sucks out K

Question 54

What are the most important components of saliva?

Answer 54

• Mucins
○ Large glycoproteins that lubricate food and facilitate swallowing
• Amylase and lingual lipase
○ Begin digestion of starches and fats
• NaHCO3
○ Helps maintain an optimal pH for enzyme activity and also to reduce Ca solubility
○ When pH is basic, less Ca loss from teeth in oral fluids
• IgA, lysozyme, lactoferrin
○ Antibacterial agents that prevent overgrowth of bacteria that require iron
○ Lactoferrin chelates iron

Question 55

Describe the cellular production of saliva

Answer 55

• Submaxillary and sublingual glands contain two types of cells
○ Serous and mucous
• Serous - fluid, electrolytes and enzymes
• Mucous - mucin secretion
• From the acinus, saliva passes relatively unchanged through a short intercalated duct
• From intercalated duct into striated duct where more epithelial cells alter the inorganic ion composition

Question 56

Saliva composition during high flow is different than low flow how?

Answer 56

• High flow - slightly hypotonic and rich in bicarbonate
  
  • Low flow - VERY hypotonic because there is time for the duct cells to modify the fluid and the duct is water impermeable

Question 57

Pancreatic secretions have what two major components?

Answer 57

• Aqueous and enzymatic components make up pancreatic secretions

Question 58

Normally, the enzymes secreted by the pancrease are inactive whilst within said pancreas. However, what is the condition called when even a small portion of those enzymes are activated too early?

Answer 58

• Autodigestion. Chain reaction of zymogens being activated and digestion of the pancreas itself. Bummer

Question 59

Chyme hits the duodenum and stimulates the release of what?

Answer 59

• CCK - cholecystokinin
  
  • 33 amino acid peptide where the 8 C-terminal residues are REQUIRED for activity
  • CCK is the most important stimulus for acinar cell secretion
  • IP3 and Ca are probably the most important 2nd messengers for CCK
  • Ach is also stimulatory for secretions

Question 60

Describe the aqueous component of pancreatic secretions and what it is useful for

Answer 60

• Mostly water and bicarbonate, produced by duct cells
• Neutralizes acid in duodenum, preventing injury to the duodenal mucosa and bringing the pH to optimum level for enzymatic digestion of chyme to proceed
○ Solvates enzymatic secretions
○ Alkalinity necessary to neutralize gastric acid dumped from stomach into small intestine
○ Presence of acid in small intestine leads to secretion from duodenal endocrine cells of secretin
○ Secretin is most important stimulus for NaHCO3
§ Thus the presence of acid in the intestine leads to secretion of a neutralizing solution
○ Secretin and CCK both inhibit gastric acid/fluid production and delay gastric emptying until intestine is ready for more

Question 61

How do duct cells produce a bicarbonate rich fluid?

Answer 61

• Similar to reverse of acid secretion by paretal cells
• HCO3 is transported into lumen and H+ is transported into interstitial fluid
• Primary active transport here is Na/K ATPase in the baslolateral membrane and H is transported into plasma by secondary active transport using energy of inward Na gradient
• Low H+ leads to high OH and thus high HCO3
• HCO3 is transported into the lumen by Cl/HCO3 exchange
• CO2 is necessary for the OH to make HCO3, and much of that comes from blood, not cellular metabolism
○ H+ into plasma will react with HCO3 and make CO2 which freely diffuses back into cell
• The water will follow the NaHCO3 net movement into the lumen

Question 62

What two signaling molecules stimulate secretion from the pancreatic duct?

Answer 62

• Secretin (through cAMP) and ach

Question 63

High flow rates produce what type of pancreatic secretion compared to low flow rates?

Answer 63

• High flow rates - HCO3 or bicarb rich fluid as there is less time to exchange this for Cl
• Low flow rates - Cl rich fluid, mostly NaCl
○ Bicarb has been replaced by Cl through exchange

Question 64

What is the primary stimulant for enzyme secretion from pancreatic acinar cells?

Answer 64

• Hormone - CCK - cholecystokinin
• Main stimulant for bicarb-rich fluid is secretin
• Vagal Ach stimulates enzyme secretion with little or no effect on the fluid composition
○ The fluid is likely influenced by peptidergic pathways like VIP

Question 65

Describe the influences that cause the three phases of pancreatic secretion

Answer 65

• Phases = cephalic, gastric and intestinal
○ Intestinal most important
• Cephalic - stimulated by Ach and maybe VIP through vagal mechanisms and brain control
• Gastric phase is stimulated by distention and vago-vagal reflexes
• Intestinal phase - food in intestine leads to increased CCK and acid in intestine is secretin secretion with vagal reflex also

Question 66

What are the constituents of saliva?

Answer 66

• Water
		○ Taste, dissolution of nutrients, aids in swallowing and speech
	• Bicarbonate
		○ Neutralizes refluxed gastric acid
	• Mucins
		○ lubrication
	• Amylase
		○ Starch digestion
	• Lysozyme, lactoferrin, IgA
		○ Innate and acquired immune protection
	• Epidermal and nerve growth fibers
		○ Contributes to mucosal growth and protection

Question 67

What, in general, is the difference in roles between the acinar cells and striated ductal cells in the salivary gland secretory unit?

Answer 67

• Acinus - creates the material that goes into the fluid

* Striated ductal cells - modify the ionic content of the fluid

Question 68

What two parasympathetic ganglia are implicated in the production of saliva?

Answer 68

• Otic ganglion
		○ Parotid gland
	• Submandibular ganglion
		○ Submandibular gland
	• Both of these are under parasympathetic stimulatory control, so Ach will stimulate saliva production

Question 69

What is the difference in saliva with either increased parasympathetic or sympathetic innervation/tone?

Answer 69

• Parasympathetic
○ Both vasodilation and secretory cell stimulation
○ Protein and fluid and ion rich solution
• Sympathetic
○ No vasodilaiton, only acinar cell secretion
○ High protein, low fluid solution

Question 70

Why is vasodiation so paramount to fluid incorporation in saliva?

Answer 70

• Fluid comes paracellularly into the glands
  
  • Without vasodilation, water has no way of getting in there
  • Saliva is primarily formed by passive filtration

Question 71

What transporters on the ductal cells allow for what electrolyte modification in saliva?

Answer 71

• Out = lumen, in = cellular and subtract from lumen
	• Na, H synporter
		○ Both in
		○ Na/k exchanger will take sodium through basolateral side and increase intracellular K concentration
	• Cl, HCO3 antiporter
		○ Cl in, bicarb out
		○ Cl will go out basolateral side
	• K/H exhanger
		○ Potassium out, acid in

Question 72

Why doesn’t more water enter the duct through the striated ductal cells?

Answer 72

• In saliva production
  
  • Salivary duct cells have tight junctions that don’t allow for paracellular movement of water
  • They do, however, have ionic transporters that modify composition

Question 73

How do the ductal cells create HCO3 to buffer the saliva?

Answer 73

• Carbonic anhydrase uses water to make CO2 into H+ and HCO3-
  
  • During low flow rates there is NaCl reabsorption with K and HCO3 secretion
  • Faster flow rates means less ionic changes

Question 74

What do Ach, secretin, and CCK do to the exocrine pancreas? (STEP)

Answer 74

• These are all NT or hormones involved in regulating exocrine pancreas secretions
• Ach
○ Vagus nerve and ENS
○ Stimulates release of digestive enzymes from acinar cells
○ Mostly cephalic stage
• Secretin
○ Released from endocrine cells in the proximal small intestines in response to acid
○ Stimulates the release of bicarb rich solution from pancreatic duct cells
• CCK (cholecystokinin)
○ Released from endocrine cells in the proximal small intestines in response to fats and proteins
○ Stimulates release of digestive enzymes from acinar cells

Question 75

What GI effects in general will the CCK cluster unit in the duodenum have when CCK is released?

Answer 75

• Overall = protein, carbohydrate, lipid adsorption and digestion
		○ Matching of nutrient delivery to digestive and absorptive capacity
	• Gallbladder
		○ contraction
	• Pancreas
		○ Acinar secretion
	• Stomach
		○ Reduced emptying
	• Sphincter of oddi
		○ relaxation

Question 76

What two peptides control CCK release at the level of the duodenal I cell?

Answer 76

• CCK-RP
○ Fatty acids hitting the cell stimulate release
• Monitor peptide
○ From pancreas, mostly Ach stimulated

Question 77

VIP and Secretin differ from the other peptides that induce acinar cell secretion how?

Answer 77

• Pancreatic (exocrine) secretion here
• VIP and secretin will influence cAMP
○ Downstream is phosph of structural and regulatory proteins
• GRP, Ach, CCK will all influence Calcium release
○ This is the more important influence on enzyme release from acinar cells

Question 78

Secretin has the main job of what?

Answer 78

• Neutralize the stomach acid
  
  • CCK will stimulate it’s release
  • It will mess with cAMP in the duct cells and increase bicarb secretion

Question 79

What is the major channel that gets choride out into the lumen of the pancreatic duct?

Answer 79

• Ductal cell secretion here in exocrine pancreas
• CFTR is the chloride channel in question
• Controlled by cAMP, thus can be regulated by secretin (stimulated release by CCK)
• Cl is important to release ductally to promote exchange with intracellular bicarb
○ Cl/HCO3 exchanger

Question 80

At a high flow rate from the pancreas, is the solution alkaline or acidic?

Answer 80

• Alkaline. This makes sense as more flow is supposed to help neutralize stomach chyme
  
  • The higher the flow rate, the more Cl and HCO3 exchange
  • Slower flow, probably can’t pump out enough Cl to stimulate exchange

Question 81

A fluid rich in KHCO3 or potassium bicarb is likely from what duct?

Answer 81

• Salivary duct

* NaHCO3 is from the pancreas

Question 82

What is true concerning the net fluid secretion in the intestines?

Answer 82

• Net fluid secretion from cells in the intestinal crypts
• HOWEVER, a net fluid reabsorption from enterocytes on the villi
○ This is because the villi surface area is way greater than the crypt surface area

Question 83

Where does the bulk of fluid reabsorption take place?

Answer 83

• In the small intestine
	• The colon is just for the last little bit, which is why increased motility on the part of the small intestine so easily overwhelms the large intestine and leads to diarrhea
	• Stomach and duodenum secrete 8L of fluid!
		○ Diet - 2
		○ Saliva - 1
		○ Gastric - 2
		○ Pancreatic - 2
		○ Bile - 1
		○ Jejunum - 1
	• Absorption
		○ Jejunum - 4.5
		○ Ileum - 3.5
		○ Colon 0.9

Question 84

Describe sodium absorption in the GI tact

Answer 84

• Sodium is absorbed all along the intestine with the most of it being in the jejunum
○ 60-80%
• Dependent on a gradient established by basolateral Na/K ATPase
• Water and sodium absorption are linked
• Na/glucose and Na/galactose and Na/amino acid transporters play a big role in sodium out of lumen into cell
○ NaCl cotransport and Na/H+ exchange are also important players

Question 85

What’s the difference between small bowel and colonic sodium absorption?

Answer 85

• In the colon Na goes through the ENaC channel

* In the small bowel, Na is absorbed mostly through co-transport of other nutrients like sugars and amino acids

Question 86

What is the difference between large and small bowel chloride absorption?

Answer 86

• Chloride is passive in proximal intestines b/c of loose tight junctions
• Chloride mostly balances the sodium charge which is moving from lumen to basolateral side
• In the colon, though, cl is specifically exchanged for HCO3 (bicarb)
○ Offsets the acidic environment of colonic bacteria

Question 87

Is potassium concentration higher intracellularly or extracellularly?

Answer 87

• Intracellular b/c of Na/K ATPase
  
  • Most of it is in the cells
  • K passively leaks out in the colon depending on speed of fluid movement
  • In diarrhea, watch for hypokalemia

Question 88

If you were to be using a magnesium based laxative for a long time, what other divalent cation might you not absorb well?

Answer 88

• Calcium and magnesium compete for uptake by enterocytes
  
  • Ca and Mg will go into enterocytes based on concentration gradient
  • The Ca concentration gradient in the cytoplasm is maintained by Ca ATPase that bumps Ca into the blood AND by the internal calcium stores within the cell (ER) that store calcium for vesicular fusion and such
  • However, magnesium isn’t so selectively maintained so lost of magnesium in the fluid makes it an osmotic laxative

Question 89

What vitamin is linked to calcium absorption?

Answer 89

• Vitamin D
  
  • After it is hydroxylated a couple times it stimulates transcription and translation of Ca-binding proteins and Ca-ATPase proteins

Question 90

Describe the fate of iron when it enters the GI system

Answer 90

• Regulated absorption in the proximal intestines
• Transported across apical membrane as either heme or Fe++
○ Receptor mediated
• Either binds to apoferritin to form ferritin that says in the cell
• OR it binds to transferrin, a carrier protein, that leaves the cell and goes into blood

Question 91

Which part of the intestine ahs the lowest degree of paracellular water permeability?

Answer 91

• The colon
  
  • Interesting to me b/c I thought large intestine was lots of water reabsorption
  • Instead, the colon wants to more finely regulate water reabsorption by altering ionic composition, not by letting water just rush back in