Gastrointestinal Physiology Flashcards
Functions of the Gastrointestinal Tract (GIT)
Transfer digested organic nutrients, minerals and water, from the external environment into the internal environment:
involves digestion and absorption
What is digestion?
Process of forming absorbable molecules from food through GIT motility, pH changes, and biological detergents/enzymes
ie breakdown food into absorbable molecules
What is absorption?
Movement of digestive food from the intestine into the blood or the lymphatic system
How does the GIT function in excretion?
(ie what is excreted from GIT)
Non-absorbable components of food, bacteria, intestinal cells, and hydrophobic molecules (drugs), cholesterol and steroids are excreted
How does the GIT function in host defense?
- Lumen of the GIT is continuous with exterior of body = outside considered to be outside the body
- The GIT forms a barrier with the outside environment and contains a highly developed immune system
- The GIT can inactivate harmful bacteria or other microorganisms
What are the 6 components of the GIT and what are the 3 accessory organs of the GIT?
6 components:
- Mouth
- Pharynx
- Esophagus
- Stomach
- Small intestine (duodenum, jejunum, ileum)
- Large intestine
3 Accessory Organs
- Pancreas
- Gall Bladder
- Liver
The top third of the esophagus is composed of _________ muscle and the rest is ________ muscle
The top third of the esophagus is composed of Skeletal muscle and the rest is smooth muscle
What are the three subsections of the mucosa?
- Epithelium - very thin layer of cells
- Lamina Propria
- Muscularis mucosa - very thin smooth mm layer
What are the four layers of the GIT?
- Mucosa (has three sublayers:
- Epithelium
- Lamina propria
- Muscularis mucosa
- Submucosa
- Muscularis externa
- Serosal layer
The connective tissue layer of the GIT is ________ and the outer muscular layer is the _______
The connective tissue layer of the GIT is serosal layer and the outer muscular layer is the muscularis externa
The epithelial cells of the mucosa are polarized, what does this mean?
They have a basolateral surface and apical surface
*there are different transport proteins on each surface
Which surface of epithelial cells is closest to the blood surface, facing away from the tube?
Basolateral surface
Which surface of the mucosal epithelium inserts the inside of the tube or lumen of the tube
Apical surface
What is the function of the epithelial layer of the mucosa (layer of the GIT)
- Selective uptake of nutrients, electrolytes and water
- Prevent passage of harmful substances
- stem cells in crypts produce daughter cells
Epithelial surface area is increased by presence of _______ and ______
Epithelial surface area is increased by presence of villi and crypts
- Villus contains a _________
- Crypt is a region which _______ into the _______
- Villus contains a single layer of epihelial cells containing microvilli
- Crypt is a region which invaginates into the lamina propria
- has stem cells
The ______ is the air passage between the pharynx and trachea
The larynx is the air passage between the pharynx and trachea
The _______ is the area around the vocal cords where air travels through
The glottis is the area around the vocal cords where air travels through
The _______ is a tissue flap that covers the trachea during swallowing
The epiglottis is a tissue flap that covers the trachea during swallowing
Swallowing is a series of ______ initiated by ______ receptors in the wall of the ________
Swallowing is a series of reflexes initiated by pressure receptors in the wall of the pharynx
How is swallowing initiated?
Pressure receptors in the pharynx are initiated by food or liquid entering the pharynx. The receptors send signals to the swallowing centre in the brainstem which signals muscles in the pharynx, the esophagus and respiratory muscles
What is happening at each letter in the image?
a) Tongue pushes food (bolus) to the back of the pharynx
b) Soft palate elevates to prevent food entering the nasal passages
- Impulses from the swallowing centre:
- inhibit respiration, raise the larynx, and close the glottis
c) Epiglottis covers the glottis to prevent food/liquid entering the trachea
d) Food descends into the esophagus
What is the upper esophageal sphincter composed of and where is it located relative to the pharynx?
- Upper esophageal sphincter is composed of a ring of skeletal muscle
- Found just inferior to the pharynx
What is the Lower Esophageal Sphincter composed of?
Where is it located?
Composed of a ring of smooth muscle
Found where the esophagus joins the stomach
At rest, are the esophageal sphincters open or closed?
Closed (both are closed except when swallowing, vomiting or burping)
What type of tissue is the esophagus composed of?
Stratified squamous epithelium
In upper third of the esophagus is _______ mm and the lower two thirds is ______ mm
In upper third of the esophagus is skeletal mm and the lower two thirds is smooth mm
What is secreted in the esophagus to lubricate and aid in the passage of food?
Mucus
What happens during the esophageal phase of swallowing?
- Upper esophageal sphincter relaxes = allows food to pass through
- sphincter closes and glottis opens to breathe again
- Peristaltic waves move the food bolus down the esophagus towards the stomach (~5-9seconds)
- Lower sphincter at the stomach opens and allows food to pass through
- Lower sphincter closes
What is the main force for the esophageal phase of swallowing?
Peristalsis (gravity assists but is NOT necessary eg can still swallow when in space or upside down)
What aids the lower esophageal sphincter in preventing gastric contents from entering the esophagus?
Equal pressure of the lower esophagus and the stomach = no pressure gradient forcing the gastric contents out
What happens when small amounts of acid enter the esophagus?
- Stimulation of peristalsis to push the acid back out
- increased salivary secretion
- aids with neutralization of the acid with saliva and clearance of the acid out of the esophagus
What three scenarios might lead to heartburn?
Lower esophageal sphincter doesn’t close properly
A big meal
Pregnancy
What are 5 functions of the stomach?
- Storage of food
- Mechanical breakdown of food
- Chemical breakdown of food
- Control rate at which food enters sm intestine
- Secretes intrinsic factor critical for absorption of Vit B12 in the ileum
What are 2 chemicals secreted by the stomach?
- Pepsinogen
- cleaved to form the enzyme pepsin
- initiates protein digestion
- cleaved to form the enzyme pepsin
- HCl
- dissolves food and partially digests macromolecules in food
Vitamin B12 is required for:
Red blood cell formation
Failure to absorb Vit B12 might result in:
Pernicious anemia and RBC deficiency
Which region of the stomachhas the most muscle?
Fundus and Body each have a thin layer of smooth mm
Antrum has a thicker smooth muscle layer
What is different between the three regions of the stomach?
- Fundus and Body
- thin layer of smooth mm
- secretes
- mucus
- pepsinogen
- HCl
- Antrum
- Thicker smooth mm layer
- Secretes
- Mucus
- Pepsinogen
- Gastrin
What controls the emptying of the stomach?
Pyloric Sphincter
A chemical messenger secreted into ducts then on to an epithelial surface without passing into blood?
Exocrine secretion
What are three major exocrine secretions in the stomach?
- Mucus
- protective coating to avoid self-digestion
- HCl
- Hydrolysis of proteins into AA, dissolving food and digesting macromolecules and sterilizing food
- Pepsinogen
- precursor to pepsin which is important for protein digestion
What are four minor secretions of the stomach?
- Intrinsic factor
- Vit B12 absorption
- Gastrin (endocrine)
- important for stimulating HCl production and increasing stomach motility
- Histamine (paracrine)
- Stimulates HCl production
- Somatostatin (paracrine)
- Inhibits HCl production
What is the function of the following four stomach secretions:
- Intrinsic factor
- Gastrin
- Histamine
- Somatostatin
What is the function of the following four stomach secretions:
- Intrinsic factor
- absorption of Vit B12
- Gastrin
- Endocrine
- hormone important for stimulating HCl production
- Increases stomach motility
- Histamine
- Paracrine
- stimulates HCl production
- Somatostatin
- Paracrine
- Inhibits HCl production
A generalized gastric gland has what five types of cells?
Include role and where they are mostly found
- Mucous cell
- Mucous neck cell
- Parietal Cell
- secretes intrinsic factor and HCl
- Found mostly in the Body/Fundus
- Chief Cell
- Secretes pepsinogen
- Enteroendocrine cell
- G-cells
- Secrete Gastrin
- Found mostly in the antrum
Where are chief cells found?
What do they secrete?
In gastric glands in all regions of the stomach
Secrete Pepsinogen (inactive precursor to pepsin)
Pepsinogen is cleaved by HCl into pepsin which accelerates protein digestion
Where are enteroendocrine cells found?
What are they also known as?
Secrete?
- Where are enteroendocrine cells found?
- gastric glands of antrum
- What are they also known as?
- G-cells
- Secrete?
- Gastrin (hormone)
- stimulates HCl production and GI motility
- Gastrin (hormone)
Which cell type would you find at the luminal end of the gastric gland?
Mucous cell
Which cell type would you find in the body and the fundus of the stomach but NOT in the antrum?
Parietal cell
What is zymogen?
Precursor for a protein that is not active and some type of chemical reaction needs to occur to make it active
What are enterochromaffin-like cells?
Where are they found?
What do they secrete?
- What are enterochromaffin-like cells?
- Found in gastric glands in all regions (more in the antrum)
- Secrete histamine
- Stimulates HCl release/production
Where are D-cells found and what do they secrete?
Found in gastric glands in all regions of the stomach but are more numerous in the Antrum
Secretes somatostatin
-regulator that negatively regulates HCl production
What is another name for parietal cell?
Oxyntic cell
What feature of parietal cells increases their surface area to maximize secretion into the stomach lumen?
Canaliculi
As the parietal cell is activated, what happens to the canaliculi?
Canaliculi become more defined,
- movement of membrane to the canaliculi
- distends them and greatly enlarges them
- proton pumps are inserted
Why is it important for parietal cells to have many mitochondria?
Need lots of ATP for active acid secretion
How does the lumen pH of the stomach compare to the cytosol pH?
Lumen pH = 1
Cytosol pH = 7
The ______ surface of the parietal cell faces the stomach lumen.
The Apical surface of the parietal cell faces the stomach lumen.
What are 7 mechanisms involved in acid secretion from the parietal cell?
- Na+/K+ ATPase
- H+/K+ ATPase
- Carbonic anhydrase
- Cl-/HCO3- exchanger
- K+ channels
- Cl+ channels
- HCl
Describe the secretion of acid from the parietal cells and include why each of the following are important:
- Na+/K+ ATPase
- H+/K+ ATPase
- Carbonic anhydrase
- Cl-/HCO3- exchanger
- K+ channels
- Cl+ channels
- HCl
Describe each of the methods of transport of the parietal cell:
- Na+/K+ ATPase
- Pumps 3 Na+ out and 2 K+ in for every molecule of ATP hydrolyzed
- establishes electrochemical gradients with a high concentration of K+ inside the cell and a high [Na+] outside the cell
- H+/K+ ATPase
- Apical/luminal membrane of the parietal cell
- Pumps out a proton (acid) into the lumen
- Primary ACTIVe Transport (ATP is hydrolyzed)
- As acid is leaving, the cell becomes more basic
- other mechanisms must prevent the cytosolic pH of the parietal cell from becoming too basic
- Carbonic anhydrase
- Parietal cell gets rid of base by removing bicarbonate
- catalyzes the formation of H2CO3 (carbonic acid) from H2o and CO2
- H2CO3 dissociates into H+ for secretion into lumen and HCO3-
- Cl-/HCO3- exchanger
- HCO3- is pumped out in exchange for a chloride ion (Cl-) secondary active transport
- K+ channels
- As protons are pumped out through the apical primary active transporter, K+ levels increase in the cytosol
- K+ channels in the apical surface open and allow K+ to leave down concentration gradient
- Loss of positive with every K+ means we must lose a negative charge to compensate thought he loss of Cl- channels
- Cl- channels
- Apical membrane
- Cl- lost into lumen of stomach as diffuses through Cl- channel
- compensates for loss of positive charge through K+ channels
- HCl
- Secreted into the lumen of the stomach as a proton leaves the cell tthough the apical H+/K+ ATPase and Cl- through the Cl- channel
How do chemical messengers regulate acid secretion?
Chemical messengers regulate the insertion of the H+/K+ ATPase into the plasma membrane of the parietal cell
What are four chemical messengers that regulate the insertion of H+/K+ ATPase into the membrane of parietal cells to regulate acid secretion?
- Gastin
- Acetylcholine
- Histamine
- Somatostatin
How do each of the four chemical messengers control insertion of H+/K+ ATPase into the membrane of parietal cells? (to regulate acid secretion)
- Gastin
- Acetylcholine
- Histamine
- Somatostatin
- Gastrin
- Gastric hormone released by G cells
- Stimulates insertion of the H+/K+ ATPase into the membrane, stimulating HCl secretion
- Acetylcholine
- Neurotransmitter
- Increased Parasympathetic activity causes the release of Ach
- increases insertion of H+/K+ ATPase into the membrane, stimulating HCl production
- Histamine
- Paracrine released from the ECL-Cell
- Stimulates insertion of the H+/K+ATPase into the membrane , stimulating acid secretion
- Somatostatin
- Paracrine released from D-cells
- Inhibits the release of HCl, gastrin and histamine
Histamine potentiates the effects of _______ and ________ to stimulate acid production
Histamine potentiates the effects of gastrin and acetylcholine to stimulate acid production
Secretion of pepsinogen from ________ cells is stimulated by _______
Secretion of pepsinogen from chief cells is stimulated by the enteric nervous system
The release of pepsinogen from the chief cell parallels:
The release of Acid from parietal cells:
What happens once pepsinogen enters the lumen?
It is cleaved and activated to pepsin by acidic pH in the stomach
What is the advantage of inactive precursor secretion (pepsinogen instead of pepsin)
Prevents digestion of self
What happens to pepsin once it enters the small intestine?
It is irreversibly inactivated
Regulation of stomach secretion is divided into what three phases?
- Cephalic Phase
- stimulation in the brain
- Gastric Phase
- when food reaches the stomach
- Intestinal Phase
- when food that has been partially broken down by the stomach enters the Sm Int.
What is the cephalic phase of gastric secretion?
- Stimulation?
- Nerve?
- Response?
What is the cephalic phase of gastric secretion?
- Stimulation?
- sight, smell, taste of food provides excitatory stimulation mainly via the:
- Nerve?
- Vagus Nerve to the stomach
- Response?
- Vagal nuclei in the brain cause the Parasympathetic nerve to release ACh at the parietal cells = stimulation of acid production
What is the Gastric Phase of Gastric Secretion?
- Major phase for regulating _______
- Stimulatory phase mediated mainly via the release of ______
- Food in the stomach causes ______ to release ______ into the blood which has what result:
What is the Gastric Phase of Gastric Secretion?
- Major phase for regulating acid production
- Stimulatory phase mediated mainly via the release of gastrin
- Food in the stomach causes G-Cells to release gastrin into the blood which has what result:
- Gastrin interacts with the parietal cell to increase acid production
What is the intestinal phase of gastric secretion?
- _______ phase
- Mainly ______ due to presence of ____, ____, _____ products and ________ in the ______-
- Mediated by:
What is the intestinal phase of gastric secretion?
- Inhibitory phase
- Mainly inhibitory due to presence of acid, fat, digestion products and hypertonic sol’ns in the duodenum
- Mediated by:
- Gastrointestinal hormones including secretin and CCK
Where are secretin and CCK secreted from and what effect do they have on Gastric Secretion?
CCK and Secretin are GI hormones secreted from epithelial cells of the Small Intestine
Enter the blood and have a negative influence on gastrin production
What four chemical messengers regulate the insertion of H+/K+ ATPase into the plasma membrane of the parietal cell?
- Gastrin
- ACh
- Histamine
- Somatostatin
What three chemical messengers stimulate the parietal cell to release acid?
ACh
Histamine
Gastrin
Starvation would occur without the ________
a) stomach
b) salivary glands
c) pancreas
Starvation would occur without the pancreas
What are four families of enzymes produced by the pancreas?
- Proteases
- protein into peptides and AA
- Amylolytic enzymes
- starch into sugars
- lipases
- triglycerides into fatty acids and monoglycerides
- nucleases
- digest nucleic acids into free nucleotides
What are acinar cells?
Cells of the pancreas that synthesize and package pancreatic enzymes (as pro-enzymes) into zymogen granules that are stored at the apical pole of the cell
What stimulates exocytosis of zymogen granules (containing pancreatic enzymes) into the lumen of the pancreatic duct?
Neurohormonal input
What enzyme embedded in the luminal membrane of the duodenum cleaves trypsinogen into trypsin?
Enterokinase - activates proenzymes from the pancreas
What is trypsin?
protease that also activates other proteases
What does the pancreas secrete to antagonize any prematurely activated trypsin?
a variety of trypsin inhibitors
What is notable about trypsin that is activated prematurely (prior to reaching the intestine)?
It can degrade itself
Proteases secreted by the pancreas
Trypsinogen
- Activated by:
- Active enzyme:
- Action
- End products
Proteases secreted by the Pancreas:
Trypsinogen
- Activated by:
- Enterokinase
- Active enzyme:
- Trypsin
- Action
- Endopeptidases (hydrolyze interior peptide bonds of proteins and polypeptides)
- End product
- Mixture of peptides and AA
Proteases secreted by the pancreas
Chymotrypsinogen
- Activated by:
- Active enzyme:
- Action
- End products
Proteases secreted by the pancreas
Chymotrypsinogen
- Activated by:
- Trypsin
- Active enzyme:
- Chymotrypsin
- Action
- Endopeptidases (hydrolyzes interior peptide bonds of proteins and polypeptides)
- End products
- Mixture of peptides and AA
Proteases secreted by the pancreas
Pro-elastase
- Activated by:
- Active enzyme:
- Action
- End products
Pro-elastase
- Activated by:
- Trypsin
- Active enzyme:
- Elastase
- Action
- Endopeptidases (hydrolyzes interior peptide bonds of proteins and polypeptides)
- End products
- Mixture of peptides and AA
Major Proteases secreted by the pancreas
Pro-carboxy peptidase A & B
- Activated by:
- Active enzyme:
- Action
- End products
Major Proteases secreted by the pancreas
Pro-carboxy peptidase A & B
- Activated by:
- trypsin
- Active enzyme:
- Carboxypeptidase A & B
- Action
- Exopeptidases (hydrolyze bonds at the C-terminal)
- End products
- Mixture of peptides and AA
What are four major proteases secreted by the pancreas?
Are they endopeptidases or exopeptidases?
- Trypsinogen - endopeptidases
- Chymotrypsinogen - endopeptidases
- Pro-elastase - endopeptidases
- Pro-carboxypeptidase A & B - exopeptidases
Endo = hydrolyzes interior peptide bonds of proteins and polypeptides
Exo = hydrolyzes bonds at the C-terminal end
What is the amylolytic enzyme secreted by the pancreas?
Function and end products?
- Pancreatic amylase
- Function
- Cleaves starches to sugars
- End-product:
- Maltose, maltriose, and alpha-limit dextrins
What are three Lipolytic enzymes secreted by the pancreas?
- Prephospholipase A2 (inactive)
- Lipase (active)
- Cholesterolesterase (active)
What is different between the breakdown of amylose by pancreatic amylase vs salivary amylase?
Nothing, identical process
Relaxation of the stomach is mediated by the __________ to the ________
Relaxation of the stomach is mediated by the parasympathetic nerves to the Enteric nervous system
Lipolytic enzymes secreted by the pancreas:
Prephospholipase A2
- Activated by
- Active Enzymes?
- Action?
- End-Products?
Lipolytic enzymes secreted by the pancreas:
Prephospholipase A2
- Activated by?
- Trypsin
- Active Enzymes?
- Phospholipase A2
- Action?
- hydrolyzes phospholipids
- End-Products?
- Free fatty acids and lysophospholipids
Lipolytic Enzymes secreted by the pancreas:
Lipase
- Activated by?
- Active Enzymes?
- Action?
- End-Products?
Lipolytic Enzymes secreted by the pancreas:
Lipase
- Activated by?
- secreted in active form
- Active Enzymes?
- already active as lipase
- Action?
- Hydrolyzes triglycerides
- End-Products?
- Free fatty acids and 2-monoglycerides
Lipolytic Enzymes secreted by the pancreas:
Cholesterolesterase
- Activated by?
- Active Enzymes?
- Action?
- End-Products?
Lipolytic Enzymes secreted by the pancreas:
Cholesterolesterase
- Activated by?
- secreted in active form
- Active Enzymes?
- Cholesterolesterase
- Action?
- Hydrolyzes cholesterol-esters
- End-Products?
- Free fatty acids and cholesterol
Where is the pyloric sphincter?
Between the antrum (of the stomach) and the duodenum (of the sm int)
Why are stomach contractions weaker in the body of the stomach than in the antrum of the stomach?
The antrum has a thicker smooth mm layer than the body
What causes the pyloric sphincter to close?
peristaltic wave in the body of the stomach and a stronger force of contraction in the antrum causes the pyloric sphincter to close
The stomach has _______ cells in the smooth muscle layer that lead to spontaneous slow waves of depolarization and repolarization
The stomach has pacemaker cells in the smooth muscle layer that lead to spontaneous slow waves of depolarization and repolarization (basic electrical rhythm)
What is the basic electrical rhythm of the stomach?
Spontaneous slow waves produced by the pacemaker cells in the smooth mm layer of the stomach (depolarization and repolarization)
Why doesn’t the basic electrical rhythm cause any contractions in the absence of neural or hormonal input?
What is their purpose?
Why doesn’t the basic electrical rhythm cause any contractions in the absence of neural or hormonal input?
- depolarizations are too small
What is their purpose?
- allows the timing of contractions
What determines the strength of stomach contraction and what determines the timing of stomach contraction?
What determines the strength of stomach contraction and what determines the timing of stomach contraction?
- Strength = amount of stimulus from neurotransmitters or excitatory hormones
- Timing = basic electrical rhythm (pacemaker cells of stomach)
Where is the “vomiting centre” located in the brain?
Medulla oblongata
What are the 5 steps of vomiting?
- Nausea, salivation, breath held in mid-inspiration
- Glottis closes off trachea
- Lower esophageal sphincter and esophagus relax
- Diaphragm and abdominal mm contract
- Reverse peristalsis moves upper intestinal contents into the stomach
- Stomach contents move up through the esophagus and out through the mouth (soft palate is raised)
What are two benefits to vomiting?
- Remove harmful substances before they are absorbed into your body
- Nausea and feeling bad associated with vomiting are negative conditioning so that if you experience these, they may prevent you from consuming the noxious substance again
What are four negative consequences of vomiting?
- Dehydration
- electrolyte imbalance
- metabolic alkalosis = pH tissue is elevated beyond normal range due to loss of acid from stomach
- Acid erosion of tooth enamel
What is a peptic ulcer?
Damage to or erosion of the GIT mucosa
- occurs in regions which are acidic such as the esophagus, stomach or the duodenum
What causes an ulcer? (3)
- Imbalance of aggressive factors (acid and pepsin) and protective factors (mucus and bicarbonate)
- Most common: bacterium Helicobacter pylori
- results in inflammation of the lining and irritation and eventually chronic inflammation and erosion
- Non-bacterial factors:
- NSAIDS
- smoking
- alcohol
- gastrinomas (rare tumour)
What problems might occur if you have a very small stomach or a stomach removed (as in gastric bypass)
- Reduction in the release of intrinsic factor = inability to absorb B12 = anemia
- Stomach is useful for reducing bacteria in your system
- Stomach regulates how much food enters the SI
What are the exocrine functions of the pancreas?
- vital for digestion
- produces secretions that enter the GIT
- Source of the majority of enzymes required for digestion of carbs, proteins, fats and nucleic acids
- Secretes bicarbonate into duodenum to neutralize HCl from stomach
What must happen in the duodenum for pancreatic digestive enzymes to be functional?
The stomach acid from the stomach must be neutralized by bicarbonate from the pancreas. Pancreatic enzymes are inactive in acidic pH
The __________ from the pancreas joins the ________ from the liver to become the _______ just before entering the duodenum
The Main pancreatic duct from the pancreas joins the common bile duct from the liver to become the hepatopancreatic sphincter (or sphincter of oddi) just before entering the duodenum
What regulates the release of both liver and pancreatic contents into the SI?
Hepatopancreatic sphincter (Sphincter of Oddi)
What is different between the secretions from the exocrine pancreas and the endocrine pancreas?
- Endocrine:
- ductless gland
- secretion occurs across the epithelial basolateral surface for diffusion into the blood
- Endocrine cells surround capillaries
- Pancreatic Islets
- Exocrine:
- secrete substances into ducts that drain onto the epithelial surface (or the apical surface) and converge into the pancreatic duct
- Secretions ultimately enter the Sm Int
- secrete substances into ducts that drain onto the epithelial surface (or the apical surface) and converge into the pancreatic duct
Pancreatic ducts have _______\_ cells at the end portion of the duct
Pancreatic ducts have acinar cells at the end portion of the duct
- Acinar cells produce and secrete digestive enzymes
- exocytosis of vesicles within the acinar cells
- Acinar cells found at the ______ portion of the ________ produce and secrete _________
- Ductal cells secrete _________ and _________
- Acinar cells found at the end portion of the pancreatic ducts produce and secrete digestive enzymes
- Ductal cells secrete bicarbonate and water
What are two primary types of cells found in pancreatic ducts?
- Acinar cells
- secrete digestive enzymes
- Ductal cells
- secrete bicarbonate and water
What is pancreatic juice composed of?
- Isotonic and alkaline (because of bicarbonate)
- Electrolytes
- High in HCO3- and low in Cl-
- [Na+] and [K+] are the same as in the plasma (hence isotonic)
- Digestive enzymes
How do the ductal cells of the pancreas produce bicarbonate and water (alkaline watery sol’n)
- Cl- channel (CFTR) at the apical surface of the ductal epithelium allows Cl- to diffuse out of the duct cell into the lumen
- Cl- that has diffused out of the duct cell is then exchanged for HCO3-
- in the pancreas, HCO3- (base) leaves the cell
- Carbonic anhydrase catalyzes the formation of carbonic acid (H2CO3)
- H2CO3 dissociates into HCO3- and H+. This HCO3- is the base that is moved into the duct lumen
- Neutral pH of cytosol is maintained by the exchange of H+ (out) for Na+ (in) via H+/Na+ exchanger
- secondary active transport pathway where the Na+ moving down its conc gradient supplies the energy to efflux H+ from the cell
- Na+ gradient is provided by the Na+/K+ ATPase
- Cl- gradient into the duct lumen draws Na+ and water paracellularly (between cells)
What is the alkaline and acid tide?
alkaline tide:
- After a meal, acid is being produced by the parietal cell and enters the lumen of the stomach
- Base leaves the cell into the bloodstream as bicarbonate (HCO3-)
- Whatever is moving into the blood = tide (therefore alkaline tide because base is moving)
- Large amount of bicarbonate is pumped across the basolateral surface into the blood = Alkaline Tide
AT THE SAME TIME:
Acid Tide:
- In the pancreas the duct cells are producing base as bicarbonate, which is moving into the lumen of the pancreatic ducts
- Large amounts of acid (H+) are being pumped across the basolateral surface into the blood stream = Acid Tide
Eventually, the base from the stomach and the acid from the pancreas meet up in the portal vein to maintain the acid-base balance of the blood stream
What cells in the pancreas synthesize and package pro-enzymes and what are the “packages” called? Where are they stored?
Acinar cells synthesize and package pro-enzymes into zymogen granules that are stored at the apical pole of the cell.
What are zymogens?
proenzymes (aka pre-cursor enzymes)
Inactive enzymes
What two types of secretory cells important in regulating pancreatic juice secretion are localized to the epithelium of the small intestine
S-cells - secretes secretin
I-cells - secrete CCK
What is happening at each number in the image:
Regulation of pancreatic secretion is mainly regulated by _________
What is happening at each number in the image:
Regulation of pancreatic secretion is mainly regulated by food & acid entering the small intestine
- Acid enters duodenum from the stomach which stimulates
-
S-cells to secrete secretin
- Secretin is a hormone released into the blood which will eventually:
- reach pancreatic duct cells and stimulate the release of bicarbonate
- important in neutralizing the acid in the duodenum which would otherwise denature pancreatic enzymes
-
AT the SAME TIME as 1-3
- Digested fat and protein in the Sm Int stimulates:
- I-cells to secrete CCK into the blood
- CCK acts on acinar cells in the pancreatic duct to stimulate
- Zymogen granules to release enzymes into the lumen
Finally, The parasympathetic nerve acts as a minor regulatory pathway and will cause the release of digestive enzymes when you are hungry and smell food
- Fatty acids and amino acids in the Sm Int trigger the secretion of _____ from ____-cells in the small intestine into the blood
- The circulating hormone released stimulates the pancreas to:
- This stimulates the gallbladder to ________
- Release of _______ for fat breakdown
- _______ relaxes
- As fats and amino acids are absorbed, the stimuli for _____ release is removed as it is the fats and AA that trigger its secretion
- Negative Feedback Loop
- Fatty acids and amino acids in the Sm Int trigger the secretion of CCK from I-cells in the small intestine into the blood
- The circulating hormone released stimulates the pancreas to: increase the secretion of digestive enzymes
- This stimulates the gallbladder to contract
- Release of bile acids for fat breakdown
- Sphincter of Oddi (hepatopancreatic sphincter) relaxes
- As fats and amino acids are absorbed, the stimuli for CCK release is removed as it is the fats and AA that trigger its secretion
- Negative Feedback Loop8
How does Secretin regulate pancreatic HCO3- Secretion?
- _____ entering the duodenum from the stomach stimulates secretin secretion from ___ cells in the SI into the blood
- Circulating secretin stimulates:
- ______ cells in the pancreas to increase bicarbonate secretion
- ______ cells in the liver to increase bicarbonate secretion
- Stomach acid is ______ thus removing the stimulation for secretin release
- Negative Feedback Loop
- Circulating secretin stimulates:
How does Secretin regulate pancreatic HCO3- Secretion?
-
Acid entering the duodenum from the stomach stimulates secretin secretion from S cells in the SI into the blood
- Circulating secretin stimulates:
- Duct cells in the pancreas to increase bicarbonate secretion
- Duct cells in the liver to increase bicarbonate secretion
- Stomach acid is neutralized thus removing the stimulation for secretin release
- Negative Feedback Loop
- Circulating secretin stimulates:
What is the common function of both Secretin and CCK?
Both CCK and Secretin inhibit gastrin secretion:
- Results in reduced stomach motility (slows stomach emptying) and reduced acid secretion
As the stomach is emptying you do Not want to produce _____ at high levels, so _____ and ____ reduce this secretion
As the stomach is emptying you do Not want to produce acid at high levels, so secretin and CCK reduce this secretion
What are the three phases of Pancreatic Secretion?
- Cephalic Phase
- Stimulation in the brain
- minor
- Sight smell and taste of food stimulate pancreatic secretion via the parasympathetic nerves
- Gastric Phase
- Minor
- Distension of the stomach will stimulate pancreatic secretion via the parasympathetic nerves
- Intestinal Phase
- MAJOR
- Acid from stomach in duodenum = secretin release
- Digested fat and protein in duodenum = CCK release
The Cl- channel involved in bicarbonate secretion in the pancreas is the same channel that is mutated in the disease ________
The Cl- channel involved in bicarbonate secretion in the pancreas is the same channel that is mutated in the disease cystic fibrosis
- this channel creates optimal secretions in the lungs
- Get thick mucus in the lungs
Cystic fibrosis patients can suffer from “________”
Cystic fibrosis patients can suffer from “Pancreatic insufficiency”
Why can patients with cystic fibrosis still produce all of the digestive enzymes?
Further, if they are still producing all of the digestive enzymes, why then can they have “pancreatic insufficiency”
How can this me overcome?
- Digestive enzymes are produced in the acinar region (the Cl- channel is mutated in the Cl-/bicarbonate and water secretion (Duct cells))
- bicarbonate and water secretion is so minimal that the produced enzymes cannot be flushed from the duct and do not reach the intestine
- Retained proteolytic (breakdown proteins) enzymes can result in autodigestion
- Patients must receive supplements of digestive enzymes and antacids to allow for adequate nutrition
- Where is the liver located?
- Where is the gallbladder located
- Below the ribcage in the Right Upper Quadrant of the Abdominal cavity
- Underneath the lobule of the liver
The main pancreatic duct and the common bile duct join to form the _______ before releasing their contents into the ____.
The release of their contents is controlled by:
The main pancreatic duct and the common bile duct join to form the ampulla of vater before releasing their contents into the duodenum
The release of their contents is controlled by: the sphincter of Oddi (hepatopancreatic sphincter)
Which two distinct routes supply the liver with blood?
How much does each route supply?
How does the make-up of blood differ between the two routes?
- Systemic circulation (via the Hepatic artery)
- ~25% of the blood volume entering the liver
- oxygenated but nutrient poor
- Hepatic portal circulation (via the Hepatic portal vein)
- ~75% of blood
- deoxygenated BUT nutrient rich
The hepatic portal vein (venous blood) and the hepatic artery (arterial blood) mix within the ________ and blood then flows through the liver toward the _____ or ______ veins which unite to carry blood back toward the inferior vena cava
The hepatic portal vein (venous) and the hepatic artery (arterial) mix within the hepatic sinusoids and blood then flows through the liver toward the hepatic or central veins which unite to carry blood back toward the inferior vena cava
What is the functional unit of the liver?
Hepatic Lobule
The hepatic lobule (functional unit of the liver) is a _______ structure with a ______ vein running through the centre and a ________ in each corner
The hepatic lobule is a hexagonal structure with a central vein running through the centre and a portal triad in each corner
What is the portal triad (of the liver)?
- Composed of branches of
- A hepatic artery
- A portal vein
- A bile duct
What are the epithelial cells of the liver called?
Hepatocytes
What is ‘unique’ about the epithelial cells of the liver compared to the classic single-layered epithelial cells that you see lining the intestine for example?
(include how bile ducts are formed)
- Hepatocytes:
- form cell-to-cell junctions considered the apical surface of the cell
- Form Tube-like structures called canaliculi networks
- conduct bile produced by hepatocytes
- Join together to form the bile ducts
What type of capillary are found in the liver?
Sinusoids:
Thin-walled capillaries with large gaps = more permeable than other types of capillary
The hepatocytes are bathed in _____ and take up ______ and _____ thereby acting as a ______
The hepatocytes are bathed in blood and take up nutrients and toxins thereby acting as a filter
Bile components produced by the hepatocytes are put into the _________ and flow towards the ______ (opposite direction of ______)
Bile components produced by the hepatocytes are put into the Canalicular network and flow towards the bile ducts (opposite direction of blood flow which occurs on the other surface of the hepatocyte)
The liver is an _____ gland that is important for the
- secretion and production of ____
- ______ and ______ of nutrients
- matches supply to demand
- ________ and ______ (oral drugs, hormones, toxins)
- Producing circulating ______
The liver is an exocrine gland that is important for the
- secretion and production of bile
-
metabolism and storage of nutrients
- matches supply to demand
- deactivation and detoxification
- Producing circulating proteins
- (eg blood coagulation factors and lipoproteins)
What are the 6 major components of bile?
- Bile acids
- made from cholesterol within the hepatocyte
- important for the emulsification of fats
- amphipathic chemicals (not enzymes)
- Cholesterol
- Salts
- sodium, potassium and bicarbonate as well as water
- Phospholipids
- important for breakdown of fat
- Bile pigments (bilirubin)
- bilirubin is important for the breakdown of heme
- Trace metals
Provide a function of each of the 6 major components of bile:
- Bile acids
- Cholesterol
- Salts
- Phospholipids
- Bile pigments (bilirubin)
- Trace metals
Provide a function of each of the 6 major components of bile:
- Bile acids
- made from cholesterol within the hepatocyte
- important for the emulsification of fats
- amphipathic chemicals (not enzymes)
- Cholesterol
- Salts
- sodium, potassium and bicarbonate as well as water
- Phospholipids
- important for breakdown of fat
- Bile pigments (bilirubin)
- bilirubin is important for the breakdown of heme
- Trace metals
Bile works in consort with the pancreatic enzyme ______
Bile works in consort with the pancreatic enzyme lipase
- lipase is water soluble
- only works on surface of lipid droplets
- bile makes the droplets smaller via emulsification
What is emulsification?
What 3 things does it require?
- Process by which bile makes a fat globule into smaller globules to allow pancreatic lipase to work
- Requires
- Mechanical disruption (GI motility)
- Emulsifying agent to prevent reaggregation (found in bile)
- Amphipathic bile salts
- Phospholipids
Bile acids form _____ with phospholipids and products of lipase digestion (free fatty acid and monoglycerides)
Bile acids form mixed micelles with phospholipids and products of lipase digestion (free fatty acid and monoglycerides)
- Why are micelle’s important?
- Fatty acids and monoglycerides are really insoluble in water
- only a few molecules exist in solution and are free to diffuse into the enterocyte
- Micelles keep monoglycerides and fatty acids in small soluble aggregates
- Equilibrium between the micelle and free fatty acid and monoglycerides
- free forms diffuse across the SI epithelium
- Micelles are like a “holding station” for small, nonsoluble lipids
- An emulsion droplet is held in solution and not allowed to re-aggregate due to the _____ and _______
- This increases the _____ for the water-soluble pancreatic ____ to have access to these fat droplets
- Lipase breaks down the triglycerides into ______ and _____
- A small number of _____ and ______ can exist in an aqueous sol’n but are rapidly absorbed by the _______ while the majority of them exist in ______
- As _____ breakdown and reform, some of the ______ and ______ are released and this allows for their ______
- An emulsion droplet is held in solution and not allowed to re-aggregate due to the bile salts and phospholipids
- This increases the surface area for the water-soluble pancreatic lipase to have access to these fat droplets
- Lipase breaks down the triglycerides into monoglycerides and fatty acids
- A small number of monoglycerides and fatty acids can exist in an aqueous sol’n but are rapidly absorbed by the SI epithelium while the majority of them exist in micelles
- As micelles breakdown and reform, some of the monoglycerides and fatty acids are released and this allows for their absorption
What are the two main cell types in the liver important for the formation of bile?
- Hepatocytes
- Produce and secrete bile acids
- also secrete phospholipids, cholesterol and bile pigments
- into bile canaliculi
- Bile duct cells
- Add bicarbonate and other salts and water to the bile
What is the role of each of the following in bile formation:
- Hepatocyte
- Bile duct cells
- Gallbladder
-
Hepatocytes
- Produce and secrete bile acids
- also secrete phospholipids, cholesterol, and bile pigments
- into bile canaliculi
-
Bile duct cells
- Add bicarbonate and other salts and water to the bile
-
Gallbladder
- stores and concentrates bile between meals and releases it when chyme enters the duodenum
Recycling of bile acids occurs through:
Enterohepatic circulation
Bile acids are produced by ________ in the liver and secreted into ________ networks
Bile acids are produced by hepatocytes in the liver and secreted into canalicular networks
What are the steps for bile acid recycling?
- Bile acids are released by the liver/gallbladder into the duodenum for fat digestion
- Bile acids are reabsorbed across the small intestine (ileum) into the portal circulation
- Bile acids are transported back into hepatocytes
Step one of Bile acid recycling:
- Bile acids are synthesized within the hepatocyte and move across the ______ surface of the hepatocyte
- Transported via a __________ into the ________ (requires ____)
- Then drain from _______ networks into _____ and then enter the gallbladder or directly into the SI
Step one of Bile acid recycling:
- Bile acids are synthesized within the hepatocyte and move across the apical surface of the hepatocyte
- Transported via a primary active transport pathway into the canalicular network (requires ATP)
- Then drain from canalicular networks into bile ducts and then enter the gallbladder or directly into the SI
Step 2 of Bile acid recycling:
- Reabsorption from the ______
- bile acids enter the small intestine lumen, digest the food and move through the SI to the terminal portion called the ______
- Bile acids move back into _______
- Bile acids are absorbed across the epithelial cell (______) through a _____
- Required to allow the bile acids to move from a region that is dilute (the ________) to a region that is more concentrated (______)
- Bile acids then move by _________ across the ______ surface of the enterocyte and into the blood
Step 2 of Bile acid recycling:
- Reabsorption from the Ileum
- bile acids enter the small intestine lumen, digest the food and move through the SI to the terminal portion called the ileum
- Bile acids move back into portal circulation
- Bile acids are absorbed across the epithelial cell (enterocytes) through a Na+-dependent secondary active transport pathway
- Required to allow the bile acids to move from a region that is dilute (the intestinal lumen) to a region that is more concentrated (enterocyte)
- Bile acids then move by facilitated transport across the basolateral surface of the enterocyte and into the blood
what is a way to prevent high cholesterol that is related to enterohepatic circulation?
Prevent reabsorption of bile acids
Step 3: transport of bile acids from blood into hepatocytes
- Bile acids are in the portal blood and are carried into the _______\_predominantly through a _________\_
- the cycle can start over again with the transport of _____\_ from the hepatocyte into the bile through a ________
Step 3: transport of bile acids from blood into hepatocytes
- Bile acids are in the portal blood and are carried into the hepatocyte predominantly through a secondary active transporter
- the cycle can start over again with the transport of bile acids from the hepatocyte into the bile through a primary active transport pathway
Hepatobiliary secretion is predominantly regulated during the intestinal phase by which three methods?
- Bile salts
- As more bile salts are absorbed from the ileum and return to the liver, more will secreted back into the bile
- Bile salt synthesis is reduced when the enterohepatic circulation is working well
- Secretin
- Controls bicarbonate production not only in the pancreas but also in the liver
- Produced and released by the S-cells in the duodenum
- Its production and release is stimulated by acid in the duodenum
- Increases bicarbonate secretion by the bile duct cell sand also in the pancreas
- CCK
- Produced by I-cells in the duodenum and jejunum
- Production stimulated by digested fats and proteins in the upper SI
- Increases contraction of the gallbladder and relaxes the sphincter of Oddi
- bile is released into the duodenum
- Produced by I-cells in the duodenum and jejunum
How do bile salts contribute to the regulation of hepatobiliary secretions during the intestinal phase?
- As more bile salts are absorbed from the ileum and return to the liver, more will be secreted back into the bile
- Bile salt synthesis is reduced when the enterohepatic circulation is working well
How does secretin contribute to hepatobiliary secretion during the intestinal phase?
- Controls bicarbonate production not only in the pancreas but also in the liver
- Produced and released by the S-cells in the duodenum
- Its production and release is stimulated by acid in the duodenum
- Increases bicarbonate secretion by the bile duct cells and also in the pancreas
How does CCK contribute to the regulation of hepatobiliary secretion during intestinal phase?
- Produced by I-cells in the duodenum and jejunum
- Production stimulated by digested fats and proteins in the upper SI
- Increases contraction of the gallbladder and relaxes the sphincter of Oddi
- bile is released into the duodenum
Gallstones are caused by excess ________
Gallstones are caused by excess cholesterol
How are gallstones formed?
- Cholesterol is insoluble in water and kept in solution in the bile through the formation of micelles with bile acids and phopholipids
- If the concentration of cholesterol in bile becomes high relative to bile acids, cholesterol starts to precipitate out, “nucleating” agent also required (ie protein, bacteria)
How are pigment gallstones formed?
With excess red blood cell breakdown (hemolysis) the amount of bile pigments are increased
Bile pigments are insoluble and concentrate in bile and form precipitates with calcium
What are the three major functions of the duodenum?
- Mixing of pancreatic digestive enzymes and bile with food
- Absorption of nutrients, iron and calcium
- Release of endocrine hormones secretin and CCK
What is the major function of the jejunum?
Digestion and absorption
- Most of the chyme entering the small intestine is digested and absorbed in the first 25% of the small intestine (duodenum and jejunum)
What is the ileum primarily involved in?
Absorption of bile acids and Vitamin B12
Where is the pyloric sphincter?
Between the stomach and small intestine
In the lumen of the small intestine are folds of _______ (circular folds)
In the lumen of the small intestine are folds of Kerckring (circular folds)
The circular folds of the small intestine are covered in _______
The circular folds of the small intestine are covered in villi
- Villus is a projection of tissue into the lumen of the tube
The surface of each individual villus in the small intestine is covered with a layer of epithelial cells whose surface membranes form small projections called _______
The surface of each individual villus in the small intestine is covered with a layer of epithelial cells whose surface membranes form small projections called Microvilli
Projections in the opposite direction of villi in the small intestine are called:
Crypt regions - invaginations of the epithelium
-Have stem cells
Where are the stem cells found in the small intestine and what are four types of epithelial cells that they differentiate into?
In the Crypts
- Paneth cells
- Endocrine cells
- Goblet cells
- Enterocytes or absorptive cells
Which type of epithelial cell in the small intestine has microvilli at the apical surface of the cell (this microvilli layer is called the “brush border membrane”)
Enterocyte (Absorptive cell)
Which type of small intestine epithelial cell is important for the secretion of mucus for the lubrication of the food and protection from acid?
Goblet Cell
What type of epithelial small intestine cell is the hormone-producing cell and what are it’s two subtypes?
Enteroendocrine cells
- I cells
- S cells
Which small intestine epithelial cell secretes antibacterial peptides which protect the GIT from bacteria?
Paneth cells
What is the brush border?
Small projections (microvilli) of epithelial cells covering the villi of the small intestine, major absorptive surface of the small intestine
What is a brush border enzyme?
Enzyme anchored to the brush border with catalytic activity in the lumen
eg enterokinase which activates trypsinogen to its active form trypsin
Brush border enzymes are important for breaking down _______ and ______ into sugars and amino acids prior to transport across the _______
Brush border enzymes are important for breaking down carbohydrates and peptides into sugars and amino acids prior to transport across the enterocyte
Digestion of Carbohydrates
- Starch (_____ and ______) is broken down into _____, ______, and ______ by salivary and pancreatic amylases
- _______ and _______ cannot be absorbed by the intestinal tract; only monosaccharides (glucose) can be absorbed
- The products of amylases are further broken down by ______ _______ ______
- Maltose/maltotriose can be digested by ______, ______ or ________ to glucose
- alpha-limit dextrins are broken down by _______ to glucose
Digestion of Carbohydrates
- Starch (amylose and amylopectin) is broken down into maltose, maltotriose and alpha-limit dextrins by salivary and pancreatic amylases
- disaccharides and trisaccharides cannot be absorbed by the intestinal tract; only monosaccharides (glucose) can be absorbed
- The products of amylases are further broken down by brush border enzymes
- Maltose/maltotriose can be digested by maltase, sucrase or alpha-dextrinase to glucose
- alpha-limit dextrins are broken down by alpha dextrinase to glucose
What is sucrose broken down into and by what?
Sucrose (disaccharide) broken down by brush border enzyme sucrase → glucose and fructose
Lactose is broken down into what? By what enzyme?
Lactose (disaccharide) broken down by brush border enzyme lactase → glucose and galactose
What 3 monosaccharides are absorbed by the GIT?
Glucose, fructose, galactose
How are glucose and galactose absorbed by the GIT (intestinal absorption of glucose and galactose)?
- Same transport pathway
- Move from the intestinal lumen into the enterocyte through the Na+ -dependent glucose transporter, SGLT (apical membrane)
- Secondary active transport as it uses the Na+ gradient to drive uptake of sugar into the enterocyte
- Na+ gradient generated by the Na+ /K+ ATPase
- Glucose and galactose are transported across the basolateral surface of the enterocyte through a facilitated glucose transporter, GLUT
How is Fructose absorbed in the GIT? (ie describe the intestinal absorption of fructose)
- Fructose moves into the enterocyte across the apical membrane through a facilitated carrier, GLUT5
- Fructose is transported across the basolateral surface of the enterocyte through a facilitated glucose transporter, GLUT2
Lumen of SI pancreatic amylase breaks down polysaccharides into 3 different products: _________, ________, __________ which are then further broken down by _________ into ________
- maltose,
- maltotriose and the
- alpha-limit dextrins
which are then further broken down by brush border enzymes into monosaccharides (Fructose, glucose, galactose)
- Fructose is carried into the enterocyte through a ______\_carrier, ______\_
- Glucose and galactose are carried into the enterocyte through a ____________pathway, ___\_
- All these monosaccharides are then absorbed across the basolateral surface of the enterocyte through a different member of the _____\_ family (facilitated glucose transporter)
- Only absorb ________ in the SI
- Fructose is carried into the enterocyte through a facilitated carrier, GLUT5
- Glucose and galactose are carried into the enterocyte through a secondary active transport pathway, SGLT
- All these monosaccharides are then absorbed across the basolateral surface of the enterocyte through a different member of the GLUT family (facilitated glucose transporter)
- Only absorb monosaccharides in the SI
What are brush border enzymes?
Brush border enzymes in the SI break down carbohydrates, and peptides into amino acids
Protein Digestion and Absorption:
- Digestion of proteins begins in the ______\_
- Pepsinogen is activated by __________to _____\_, which breaks down proteins
- In the small intestine proteins are broken down by pancreatic proteases (Major ones are ______\_and ________\_)
- Further broken down to free amino acids by:
- ________\_ – pancreatic protease
- _______\_ – brush border enzyme
- Many other _________\_
- Trypsin and chymotrypsin can only cleave the ______\_peptide bonds, while carboxypeptidase and aminopeptidase can cleave the _______\_ and the ________\_ peptide bonds
- Free amino acids are absorbed by _________\_coupled to ___\_ (many different transport pathways)
- Small peptides (dipeptides or tripeptides) can also be absorbed by ___________coupled to __\_ (rather than Na+)
- Once the peptides are absorbed by the cell, ___________ break down the peptides into individual amino acids
Protein Digestion and Absorption:
- Digestion of proteins begins in the stomach
- Pepsinogen is activated by stomach acid to pepsin, which breaks down proteins
- In the small intestine proteins are broken down by pancreatic proteases (Major ones are trypsin and chymotrypsin)
- Further broken down to free amino acids by:
- Carboxypeptidase – pancreatic protease
- Aminopeptidase – brush border enzyme
- Many other brush border enzymes
- Trypsin and chymotrypsin can only cleave the internal peptide bonds, while carboxypeptidase and aminopeptidase can cleave the amino-portion and the carboxyterminal peptide bonds
- Free amino acids are absorbed by secondary active transport coupled to Na+ (many different transport pathways)
- Small peptides (dipeptides or tripeptides) can also be absorbed by secondary active transport coupled to H+ (rather than Na+)
- Once the peptides are absorbed by the cell, intracellular peptidases break down the peptides into individual amino acids
Protein Digestion and Absorption:
- Amino acids undergo ________\_across the _____\_ surface of the enterocyte into the circulation
- Many different ______\_at the apical surface and _______\_ transporters at the basolateral surface specific for different amino acids
Protein Digestion and Absorption:
- Amino acids undergo facilitated diffusion across the basolateral surface of the enterocyte into the circulation
- Many different secondary active transporters at the apical surface and facilitative transporters at the basolateral surface specific for different amino acids
Summary of Digestion and Absorption of Proteins:
- Proteins and peptides are acted on by in the stomach
- is released by chief cells and then activated by the of the lumen of the stomach
- continue to breakdown peptides into amino acids and smaller peptides in the duodenum
- cleave peptides into amino acids
- Amino acids can be reabsorbed and taken up by the enterocyte via a
- Small peptides can also be taken up by a coupled to
- Small peptides are cleaved within the cell by to amino acids
- Amino acids can then undergo out of the cell into the interstitial space for absorption into the bloodstream
Summary of Digestion and Absorption of Proteins:
- Proteins and peptides are acted on by pepsin in the stomach
- Pepsinogen is released by chief cells and then activated by the acidic pH of the lumen of the stomach
- Pancreatic proteases continue to breakdown peptides into amino acids and smaller peptides in the duodenum
-
Brush border peptidases cleave peptides into amino acids
- Amino acids can be reabsorbed and taken up by the enterocyte via a Na+ - dependent process
- Small peptides can also be taken up by a secondary active transport coupled to H+
- Small peptides are cleaved within the cell by intracellular peptidases to amino acids
- Amino acids can then undergo facilitated diffusion out of the cell into the interstitial space for absorption into the bloodstream
________ are composed of lipid molecules that arrange themselves in a spherical form in aqueous solutions
Micelles are composed of lipid molecules that arrange themselves in a spherical form in aqueous solutions
Micelles are formed by:
Formed from fatty acids, monoglycerides and bile salts during fat digestion in the SI
Large fat droplets are composed mostly of ________
Large fat droplets are composed mostly of triglycerides
- Lipid droplets are emulsified through the combined action of ________\_and ________\_ which allows ________\_to release ________\_ and ________\_
-
________\_is water-soluble and can only act on the surface of the ________\_; large fat droplets must be broken down into smaller ones for ________\_ to act
- ________\_and ________\_ bind to the outside of the smaller droplets to keep them from re-aggregating
- Pancreatic lipase can then break triglycerides into ________\_and ________\_; these products of lipase digestion are incorporated into micelles, which are in a dynamic state of breaking down and reforming
-
________\_is water-soluble and can only act on the surface of the ________\_; large fat droplets must be broken down into smaller ones for ________\_ to act
- Lipid droplets are emulsified through the combined action of mechanical disruption and bile acids/phospholipids which allows pancreatic lipase to release free fatty acids and monoglyceride
-
Pancreatic lipase is water-soluble and can only act on the surface of the fat droplets; large fat droplets must be broken down into smaller ones for pancreatic lipase to act
- Bile acids and phospholipids bind to the outside of the smaller droplets to keep them from re-aggregating
- Pancreatic lipase can then break triglycerides into monoglycerides and free fatty acids; these products of lipase digestion are incorporated into micelles, which are in a dynamic state of breaking down and reforming
-
Pancreatic lipase is water-soluble and can only act on the surface of the fat droplets; large fat droplets must be broken down into smaller ones for pancreatic lipase to act
Once the epithelial cells absorb the fatty acids and monoglycerides, they are processed by the _________\_back into ______\_
Once the epithelial cells absorb the fatty acids and monoglycerides, they are processed by the endoplasmic reticulum back into triglycerides
Why are fatty acids and monoglycerides resynthesized into triglycerides as they pass through the epithelial cell?
- To maintain the diffusion gradient from the lumen of the small intestine to the epithelial cell, so that fatty acids and monoglycerides can be absorbed into the enterocytes by diffusion
- To allow triglycerides to be further processed for absorption
- Within the ER, triglycerides aggregate into lipid droplets that are coated with amphipathic proteins; the droplets of triglycerides are then packaged in the Golgi and secreted across the basolateral surface of the enterocyte through exocytosis
Extracellular fat droplets known as “________\_”
Extracellular fat droplets known as “chylomicrons”
Why are fatty acids and monoglycerides resynthesized into triglycerides as they pass through the epithelial cell?
- To maintain the ____________from the lumen of the small intestine to the epithelial cell, so that fatty acids and monoglycerides can be absorbed into the enterocytes by diffusion
- To allow _________\_ to be further processed for absorption
- Within the _________\_, triglycerides aggregate into _________\_ that are coated with _________\_; the droplets of triglycerides are then packaged in the _________\_ and secreted across the _________\_ surface of the enterocyte through exocytosis
- Extracellular fat droplets known as “_________\_”
Why are fatty acids and monoglycerides resynthesized into triglycerides as they pass through the epithelial cell?
- To maintain the diffusion gradient from the lumen of the small intestine to the epithelial cell, so that fatty acids and monoglycerides can be absorbed into the enterocytes by diffusion
- To allow triglycerides to be further processed for absorption
- Within the ER, triglycerides aggregate into lipid droplets that are coated with amphipathic proteins; the droplets of triglycerides are then packaged in the Golgi and secreted across the basolateral surface of the enterocyte through exocytosis
- Extracellular fat droplets known as “chylomicrons”
Chylomicrons contain (4)
- triglycerides,
- phospholipids,
- fat-soluble vitamins and
- cholesterol
Chylomicrons are absorbed by the ________\_via _____\_
Chylomicrons are absorbed by the lymphatic system via lacteals
Why are chylomicrons absorbed via lacteals instead of capillaries?
lacteals are leakier than capillaries
Lacteal → lymphatic vessel in the intestinal villi
Chylomicrons absorbed into the lymphatic system eventually enter systemic circulation through:
o The lymphatics eventually enter into the systemic circulation via the thoracic duct
How are fatty acids and monoglycerides released from triglycerides in chylomicrons for absorption by tissues?
Components of fat move from the blood into the tissue; a lipase (lipoprotein lipase) found on endothelial cells of blood vessels then breaks down triglycerides present in chylomicrons to monoglycerides and free fatty acids to be taken up by tissues
______\_iron or Fe2+ (_____\_ iron)is absorbed by the GIT
Divalent iron or Fe2+(ferrous iron)is absorbed by the GIT
How is divalent iron absorbed into the enterocyte?
- Divalent iron is actively transported into the enterocyte through an __________
- Once divalent iron is actively transported into the intestinal epithelial cells it binds with a protein called _______
- _____ is a protein iron complex that acts as a storage form of iron
- The absorbed iron that does not bind to ____ to be stored in the epithelial cell is released on the blood side of the enterocyte and transported in the blood attached to a plasma protein called ______
- Divalent iron is actively transported into the enterocyte through an apical transport pathway
- Once divalent iron is actively transported into the intestinal epithelial cells it binds with a protein called ferritin
- Ferritin is a protein iron complex that acts as a storage form of iron
- The absorbed iron that does not bind to ferritin to be stored in the epithelial cell is released on the blood side of the enterocyte and transported in the blood attached to a plasma protein called transferrin
Absorption of Iron from the Intestine:
- Iron that remains in the enterocyte bound to ______ is excreted from the body when the enterocytes slough off of the villi tips
- When body stores of iron are high, the production of ferritin is _____, resulting in:
- When the intestinal cells are sloughed off, the iron is excreted in the feces
- When there is a need for iron and iron stores are depleted, the enterocytes produce ___ ferritin resulting in:
- Iron that remains in the enterocyte bound to ferritin is excreted from the body when the enterocytes slough off of the villi tips
- When body stores of iron are high, the production of ferritin is high, resulting in: increased binding of ferritin in the epithelial cells and a reduction in the amount of iron released into the blood
- When the intestinal cells are sloughed off, the iron is excreted in the feces
- When there is a need for iron and iron stores are depleted, the enterocytes produce less ferritin resulting in: less iron retained in the enterocyte and more will then be absorbed into the blood
Which region of the GIT is responsible for the most fluid reabsorption?
The small intestine
Absorption and Secretion of Water: Generalizations:
- In the small intestine water absorption occurs at the ____\_while secretion occurs at the ____\_
- Intestinal epithelium establishes an _______\_and water follows through ______\_ (Paracellular transport)
- The gradient has to be in the inward direction for _____\_to occur and in the outward direction for ______\_ to occur
Absorption and Secretion of Water: Generalizations:
- In the small intestine water absorption occurs at the villi while secretion occurs at the crypts
- Intestinal epithelium establishes an osmotic gradient and water follows through tight junctions (Paracellular transport)
- The gradient has to be in the inward direction for absorption to occur and in the outward direction for secretion to occur
It is important to understand electrolyte transport to understand water transport
- ____\_, ____\_ and ______\_ are important electrolytes for water transport
It is important to understand electrolyte transport to understand water transport
- Sodium, chloride and bicarbonate are important electrolytes for water transport
Absorption of Water in the Small Intestine predominantly depends on _____\_ generated during secondary active nutrient uptake (________)
Absorption of Water in the Small Intestine predominantly depends on Na+ gradients generated during secondary active nutrient uptake (glucose or amino acids)
Absorption of Water in the Small Intestine:
- ______\_generates a low intracellular Na+ concentration, pumping Na+ out of the cell; this Na+ gradient is used to move ____\_ into the cell
- In the case of glucose, glucose and Na+ are brought in by the ________\_and then pumped out by the ________\_
- The Na+ gradient from low to high results in ____\_, a negatively charged ion, following the positively charged Na+
- Water then follows those two gradients
Absorption of Water in the Small Intestine:
- Na+ /K+ ATPase generates a low intracellular Na+ concentration, pumping Na+ out of the cell; this Na+ gradient is used to move glucose into the cell
- In the case of glucose, glucose and Na+ are brought in by the Na+ -glucose transporter SGLT and then pumped out by the Na+ /K+ ATPase
- The Na+ gradient from low to high results in Cl- , a negatively charged ion, following the positively charged Na+
- Water then follows those two gradients
Water absorption in the LI is very similar to the SI, relying on the movement of __\_ from the lumen to the extracellular fluid
- With what important difference******
- Water absorption in the LI is very similar to the SI, relying on the movement of Na+ from the lumen to the extracellular fluid
- Importantly, there are no nutrients (glucose) being absorbed in a healthy LI, so the transport pathway is a little different
Secretion of Water in the SI predominantly depends on:
Secretion of Water in the SI predominantly depends on Cl- gradients generated by secondary active Na+ /K+ /2Cl- transporter (NKCC1)
Secretion of Water in the SI:
- Depends on __\_gradients generated by ___\_
- NKCC1 transports 3 ions: ___\_, __\_ and _\_
- NKCC1 allows the accumulation of __\_in the enterocyte based on the inwardly-directed __________\_
- ____\_on the brush border membrane of the epithelial cell opens, to allow Cl- to move down its concentration gradient into the _____\_
- ___\_ will be attracted to the negative gradient of Cl- and water will follow, being secreted into the lumen
- cAMP:
- Stimulates the opening of ____\_
Secretion of Water in the SI:
- Depends on Cl- gradients generated by NKCC1
- NKCC1 transports 3 ions: Na+ , K + and Cl-
- NKCC1 allows the accumulation of Cl- in the enterocyte based on the inwardly-directed Na+ electrochemical gradient
- CFTR on the brush border membrane of the epithelial cell opens, to allow Cl- to move down its concentration gradient into the intestinal lumen
- Na+ will be attracted to the negative gradient of Cl- and water will follow, being secreted into the lumen
- cAMP:
- Stimulates the opening of CFTR
*CFTR = Cystic fibrosis transmembrane conductance regulator
How does secretion of water by the LI differ to secretion of water in the SI?
They are identical:
- Secretion of Water in the SI:
- Depends on Cl- gradients generated by NKCC1
- NKCC1 transports 3 ions: Na+ , K + and Cl-
- NKCC1 allows the accumulation of Cl- in the enterocyte based on the inwardly-directed Na+ electrochemical gradient
- CFTR on the brush border membrane of the epithelial cell opens, to allow Cl- to move down its concentration gradient into the intestinal lumen
- Na+ will be attracted to the negative gradient of Cl- and water will follow, being secreted into the lumen
- cAMP:
- Stimulates the opening of CFTR
- Depends on Cl- gradients generated by NKCC1
Most common motion in the SI during digestion is _______\_
Most common motion in the SI during digestion is segmentation
Why is segmentation important?
Allows for the mechanical breakdown of food (increase the surface area) and mixing of the food with digestive enzymes and water
- Frequency of contraction set by _______\_, driven by the ____\_ cells in the smooth muscle layers
- 12 contractions/min in ___\_
- 9 contractions/min in ___\_
- The contraction force of the smooth muscle is determined by ______\_
- Results in a ____\_ net migration towards the LI
- Slow passage of food allows for _________\_
- Frequency of contraction set by basic electrical rhythm, driven by the pacemaker cells in the smooth muscle layers
- 12 contractions/min in duodenum
- 9 contractions/min in ileum
- The contraction force of the smooth muscle is determined by neurohormonal input
- Results in a very small net migration towards the LI
- Slow passage of food allows for digestion and absorption of nutrients
Peristaltic activity is referred to as the:
Peristaltic activity is referred to as the migrating myoelectric complex (MMC)
Purpose of Migrating myoelectric complex (MMC)?
push undigested material from the SI into the LI and prevents bacteria from remaining in the SI
What regulates the migrating myoelectric complex?
Intestinal hormone motilin
- Initiates the MMC
- When you eat, motilin release is inhibited to allow the segmentation contractions to occur
What happens to motilin release when you eat?
Motilin is an intestinal hormone that initiates the MMC (peristaltic contractions).
It’s release is inhibited when you eat in order to allow segmentation contractions to occur
What causes cholera?
What are the symptoms?
What is the physiological impact of the bacteria causing cholera?
- Cause
- eating food or drinking water contaminated with the bacteria Vibrio cholera
- Symptoms
- Vomiting and excessive diarrhea
- 20 litres of stool per day (normal 0.1 litres), dehydration, electrolyte imbalance, death
- Vomiting and excessive diarrhea
- Physiological impact:
- Vibrio cholerae produce a toxin that increases the production of cAMP
- Increased cAMP stimulates the Cl- channel present in the SI epithelia to open, allowing large amount of Cl- into the intestinal lumen; water follows and is lost as diarrhea
- Vibrio cholerae produce a toxin that increases the production of cAMP
_______\_: sphincter between the cecum and the ileum
Ileocecal valve: sphincter between the cecum and the ileum
The ileocecal valve is ___\_when the ileum contracts after a meal and ___\_ when the LI is distended
The ileocecal valve is open when the ileum contracts after a meal and closed when the LI is distended; retains large intestine contents including bacteria
Functions of the Ascending, transverse, descending, & sigmoid colon
- Re-absorption of water
- Majority of water absorption occurs in the SI, but these regions do absorb water
- Serve as a reservoir for the storage of waste and undigested materials prior to elimination by defecation
- Absorb products of bacterial metabolism
Anus:
- Composed of two sphincters that control ____\_
- Internal anal sphincter: ________ (type of muscle)
- External anal sphincter: ________ (muscle?)
Anus:
- Composed of two sphincters that control defecation
- Internal anal sphincter: smooth muscle/involuntary
- External anal sphincter: skeletal muscle/under voluntary control
What is one reason why the surface area of the large intestine is much smaller than the small intestine?
The large intestine only has crypts (no villi)
- crypts have stem cells
4 different epithelial cells generated from the stem cells in the Large intestine:
Stem cells in the crypts of the LI differentiate into one of:
- Absorptive cells (enterocytes) → similar to the SI but do not contain brush border enzymes
- Goblet cells → abundant
- Endocrine cells → very few
- Paneth cells → very few
What are three functions of the bacteria in the Large Intestine (colonic bacteria)?
- Metabolize fiber into short chain fatty acids that are absorbed by diffusion
- Can also produce vitamins (Vitamin K) that are absorbed
- Produce gas
Absorption of water in SI occurs predominantly over the ___\_ surface whereas water absorption in the LI occurs predominantly in the _____
Absorption of water in SI occurs predominantly over the villi surface whereas water absorption in the LI occurs predominantly in the _crypts (_no villi in large intestine)
What are the two types of movement in the Large intestine?
- Mixing:
-
Segmentation in the LI
- Slower basal electrical rhythm than SI to allow retention in the colon
-
Segmentation in the LI
- Propulsion:
- Wave of propulsion or intense contraction (mass movement) spreads rapidly over the LI, pushing the contents towards the anus; this happens after eating and prior to defecation
What initiates defecation?
Process of defecation initiated by the mass movement of the large intestine contents into the rectum
Describe the defecation reflex:
- Process of defecation initiated by the mass movement of the large intestine contents into the rectum
- Rectum distends and activates mechanoreceptors o
- A reflex is initiated:
- Rectum contracts, internal anal sphincter relaxes and outer anal sphincter contracts (Initially)
- Increased peristaltic activity in the sigmoid colon, increasing pressure results in reflex relaxation of the external anal sphincter
- Feces voided
- After toilet training, the brain can override this reflex relaxation of the outer sphincter, delaying defecation to a more socially acceptable time
- Delay results in reverse peristalsis and rectal contents are moved back into the sigmoidal colon
- Disadvantage of delay is more water absorption occurs and feces will become harder to void
