Case 3 Flashcards
what are pancreatic digestive enzymes secreted by?
pancreatic acini
where is large volumes of sodium bicarbonate solution secreted by?
the small ductules (duct cells) and larger ducts leading from the acini
what leaves the pancreas and how?
The combined product of enzymes and sodium bicarbonate (pancreatic juice) then flows through a long pancreatic duct that normally joins the hepatic/bile duct immediately before it empties into the duodenum through the papilla of Vater, surrounded by the sphincter of Oddi.
what is pancreatic juice secreted most abundantly in response to? what determines the characteristics of the pancreatic juice
the presence of chyme in the duodenum
• The characteristics of the pancreatic juice are determined to some extent by the types of food in the chyme.
what is the endocrine function of pancreas? what secreted from where?
- Insulin is secreted by beta-cells of the islet of Langerhans.
- Glucagon is secreted by alpha-cells of the islet of Langerhans.
- Insulin and glucagon is secreted directly into the blood.
what is the fundamental secretory unit composed of?
an acinus and an intercalated duct
how do intercalated ducts arrive at main pancreatic duct?
Intercalated ducts merge to form intralobular ducts, which, in turn, merge to form interlobular ducts, and then the main pancreatic duct.
what do pancreatic secretions contain?
- Digestive enzymes - proteins, carbohydrates and fats.
- Bicarbonate ions (large quantities) – neutralisation of the acidity of the chyme emptied from the stomach into the duodenum.
- Water
what are the three protein digestive enzymes secreted by the pancreas?
- Trypsin – the most abundant of the protein digestive enzymes to be secreted. It splits whole and partially digested proteins into peptides of various sizes but do not cause release of individual amino acids.
- Chymotrypsin - It splits whole and partially digested proteins into peptides of various sizes but do not cause release of individual amino acids.
- Carboxypolypetidase - this splits peptides into individual amino acids, thus completing the digestion of some proteins all the way to the amino acid state.
when first synthesised in the pancreatic cells, what form are these proteolytic digestive enzymes in? what is this called? what are they called? and how is each activated? when do they become activated?
• When first synthesized in the pancreatic cells, the proteolytic digestive enzymes are in the inactive forms ( termed ‘zymogens’) which are inactive enzymatically:
1. Trypsinogen
o Activated by the enzyme enterokinase (secreted by the intestinal mucosa when chyme comes into contact with the mucosa).
o It can also be autocatalytically activated by trypsin that has already been formed from previously secreted trypsinogen.
2. Chymotrypsinogen
o Activated by trypsin to form chymotrypsin.
3. Procarboxypolypeptidase
o Activated by trypsin to form carboxypolypeptidase.
• They become activated only after they are secreted into the intestinal tract.
what is the carbohydrate digestive enzyme secreted by the pancreas? what does it do?
pancreatic amylase
• This hydrolyses starches, glycogen, and other carbohydrates (except cellulose) to form mostly disaccharides and a few trisaccharides.
what are the three fat digestive enzymes secreted by the pancreas?
- Pancreatic Lipase – this hydrolyses neutral fat into fatty acids and monoglycerides.
- Cholesterol Esterase – this causes hydrolysis of cholesterol esters.
- Phospholipase – this splits fatty acids from phospholipids.
what do proteases help keep the intestine free of?
parasites such as bacteria, yeast and protozoa
what might a shortage of amylase cause?
• Diarrhoea due to the effects of undigested starch in the colon.
what can lack of lipase cause?
- Lack of needed fats and fat-soluble vitamins.
* Diarrhoea and/or fatty stools.
what does the exocrine pancreas have a large store of?
digestive enzymes for carbohydrates and proteins, but not for lipids.
what does trypsin inhibitor do?
prevents digestion of the pancreas itself.
• It is important that the proteolytic enzymes of the pancreatic juice do not become activated until after they have been secreted into the intestine because the trypsin and the other enzymes would digest the pancreas itself.
which cells secrete trypsin inhibitor? what does it do in the pancreas?
• The cells that secrete proteolytic enzymes also secrete trypsin inhibitor.
This substance is formed in the cytoplasm of the glandular cells, and it prevents activation of trypsin both inside the secretory cells and in the acini and ducts of the pancreas.
As trypsin activates the other pancreatic proteolytic enzymes, trypsin inhibitor prevents activation of the others as well.
how can acute pancreatitis take place?
- When the pancreas becomes severely damaged or when a duct becomes blocked, large quantities of pancreatic secretion sometimes become pooled in the damaged areas.
- Under these conditions, the effect of trypsin inhibitor is often overwhelmed, in which case the pancreatic secretions rapidly become activated, thus causing digestion of the pancreas, giving rise to the condition called acute pancreatitis.
what are the protective factors against acinar cell autodigestion? what are their mechanisms?
- Packaging of many digestive proteins as zymogens = precursor proteins lack enzymatic activity
- Selective sorting of secretory proteins and storage in zymogen granules = restricts the interaction of secretory proteins with other cellular compartments
- Protease inhibitors in the zymogen granule = block the action of prematurely activated enzymes
- Condensation of secretory proteins in low pH = limits the activity of active enzymes
- Nondigestive proteases = degrade active enzymes
what is the concentration of bicarbonate ions in pancreatic juice? why is this important?
- Upon stimulation of the pancreas to secrete copious quantities of pancreatic juice, the bicarbonate ion concentration can rise to five times (145 mEq/L) its concentration in the plasma.
- This provides a large quantity of alkali in the pancreatic juice that serves to neutralize the hydrochloric acid emptied into the duodenum from the stomach.
describe the secretion of sodium carbonate solution
- Carbon dioxide diffuses into the ductal cell from the blood:
Under the influence of carbonic anhydrase, it combines with water to form carbonic acid (H2CO3).
The carbonic acid in turn dissociates into bicarbonate ions and hydrogen ions (HCO3- and H+).
o Some HCO3- ions also enter the cell directly across the basolateral membrane via an Na/HCO3 cotransporter.
Then the bicarbonate ions are actively transported into the lumen via a Cl-HCO3 exchanger. - The hydrogen ions are exchanged for sodium ions through the blood border of the cell by a secondary active transport process.
This supplies the sodium ions (Na+) that are transported through the luminal border into the pancreatic duct lumen to provide electrical neutrality for the secreted bicarbonate ions. - The overall movement of sodium and bicarbonate ions from the blood into the duct lumen creates an osmotic pressure gradient that causes osmosis of water also into the pancreatic duct, thus forming an almost completely isosmotic bicarbonate solution.
- Some sodium ions (Na+) enter the lumen through the tight junctions due to the negative voltage of the lumen.
what are the three basic stimuli important in causing pancreatic secretion?
- Acetylcholine (M3 receptors) - released from the parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system.
- Cholecystokinin (CCK) – secreted by the duodenal and upper jejunal mucosa in response to presence of fats and amino acids.
- Secretin - secreted by the duodenal and jejunal mucosa in response to the presence of highly acid food in the small intestine.
what do ACh and CCK stimulate in the pancreas?
stimulate the acinar cells to secrete large quantities of pancreatic digestive enzymes but relatively small quantities of water and electrolytes to go with the enzymes.
without water in the duct what happens?
Without the water, most of the enzymes remain temporarily stored in the acini and ducts until more fluid secretion comes along to wash them into the duodenum.
what does secretin stimulate?
stimulates ductal epithelial cells to secrete of large quantities of water solution of sodium bicarbonate.
what happens when these stimuli (ACh, CCK and secretin) for pancreas all occur at once?
- When these stimuli all occur at once, the total secretion is far greater than the sum of the secretions caused by each one separately.
- Therefore, the various stimuli are said to ‘multiply’, or ‘potentiate’ on another.
what are two pancreatic acinar cell pathways for stimulating the insertion of zymogen granules and thus releasing digestive enzymes?
- ACh and CCK both activate Gαq, which stimulates PLC, which ultimately leads to the activation of PKC and the release of Ca2+.
- Elevated [Ca2+]i also activates calmodulin (CaM), which can activate protein kinases (PK) and phosphatases (PP).
- Finally, VIP and secretin both activate Gαs, which stimulates adenylyl cyclase (AC), leading to the production of cAMP and the activation of PKA.
what do duct cells have receptors for? what do these substances do?
- The duct cells have receptors for secretin, GRP (gastrin-releasing peptide), all of which stimulate HCO3- secretion.
- The duct cells have receptors for substance P which inhibits HCO3- secretion.
cephalic phase of pancreatic secretion
- what are the simuli
- which most important
- what does it cause
- how
- The sight, taste, or smell of food stimulates pancreatic acinar cells, through the vagus nerve and M3 receptors (acetylcholine)(biggest stimulus to get pancreas working), to release digestive enzymes, and to a lesser extent, stimulates duct cells to secrete HCO3- and fluid.
- However, only a small amount of the secretion flows immediately through the pancreatic ducts into the intestine because only small amounts of water and electrolytes are secreted along with the enzymes.
- VIP (vasoactive intestinal peptide)
- GRP (gastrin releasing peptide)
gastric phase of pancreatic secretion
- how does the presence of food modulate pancreatic secretion
- how does the presence of food in the stomach affect pancreatic secretions
- how important
• The presence of food modulates pancreatic secretion by:
- Affecting hormone release
- Stimulating neural pathways
- Modifying pH and availability of nutrients in the proximal part of the small intestine
• The presence of food in the stomach stimulates pancreatic secretions – primarily from the acinar cells – through two routes:
- Distention of the stomach activates a vagovagal reflex.
- Protein digestion products (peptones) stimulate G-cells in the antrum of the stomach to release gastrin, which is a poor agonist of the CCKA receptors on acinar cells.
- VIP
- GRP
- gastric phase smaller component
intestinal phase of pancreatic secretion
- what stimulates this
- what does it cause
- how important
- Protein and lipid breakdown products stimulate a vagovagal reflex that stimulates primarily the acinar cells.
- The acidity of the chyme stimulates S-cells in the duodenum to secrete secretin, which acts on receptors on duct cells, stimulating HCO3- secretion (main effect in this phase).
- Protein and lipid breakdown products stimulate I-cells in duodenum to secrete CCK, which acts on receptors on acinar cells, stimulating enzyme secretion.
- most important stimulus to get pancreas working – responsible for 80% of what pancreas produces
what percentage of maximum enzyme secretion does each phase in pancreatic secretion cause?
cephalic = 25% gastric = 10-20% intestinal = 50-80%
secretin
- what is it
- forms
- what cells
- when released
- what does it cause
- Secretin is a polypeptide, containing 27 amino acids, present in an inactive form, prosecretin, in so-called S-cells in the duodenal and jejunal mucosa.
- When acid chyme with pH less than 4.5 to 5.0 enters the duodenum from the stomach, it causes duodenal mucosal release and activation of secretin, which is then absorbed into the blood.
- The constituent of chyme that causes this secretin release is the HCl from the stomach.
- Secretin in turn causes the pancreas to secrete large quantities of fluid containing a high concentration of bicarbonate ion (up to 145mEq/L) but a low concentration of chloride ion.
what are the functions of sodium bicarbonate secretion?
• Sodium bicarbonate causes neutralization of the HCl.
• This is followed by another reaction in the duodenum: HCl +NaHCO3»_space;> NaCl +H2CO3
Then the carbonic acid immediately dissociates into carbon dioxide and water.
The carbon dioxide is absorbed into the blood and expired through the lungs, thus leaving a neutral solution of sodium chloride in the duodenum.
In this way, the acid contents emptied into the duodenum from the stomach become neutralized, so that further peptic digestive activity by the gastric juices in the duodenum is immediately blocked.
Because the mucosa of the small intestine cannot withstand the digestive action of acid gastric juice, this is an essential protective mechanism to prevent development of duodenal ulcers.
• Bicarbonate ion secretion by the pancreas provides an appropriate pH for action of the pancreatic digestive enzymes, which function optimally in a slightly alkaline or neutral medium, at a pH of 7.0 to 8.0.
The pH of the sodium bicarbonate secretion averages 8.0.
cholecystokinin
- what is it
- what cells where
- what stimulates release
- what causes
• Cholecystokinin (CCK) is a polypeptide containing 33 amino acids.
• It is released by I-cells in the duodenal and upper jejunal mucosa.
• This release of CCK results especially from the presence of proteoses and peptones (products of partial protein digestion) and long-chain fatty acids in the chyme coming from the stomach.
• CCK, like secretin, passes by way of the blood to the pancreas, where it binds to CCKA receptors causing secretion of pancreatic digestive enzymes by the acinar cells.
• This accounts for 70-80% of the total secretion of the pancreatic digestive enzymes after a meal.
• Picture:
Intense sodium bicarbonate secretion in response to acid in the duodenum, stimulated by secretin.
A dual effect in response to soap (a fat).
Intense digestive enzyme secretion (when peptones enter the duodenum) stimulated by cholecystokinin.
what enzymes for hydrolysis of disaccharides and small glucose polymers are there in the enterocytes lining the villi of the small intestine?
- Lactase: split lactose into galactose and glucose.
- Sucrase: split sucrose into fructose and glucose.
- Maltase: split maltose into multiple molecules of glucose.
- α-dextrinase: split small glucose polymers into multiple molecules of glucose.
where are the enzymes located in small intestine?
in the enterocytes covering the intestinal microvilli brush border, so that the disaccharides are digested as they come in contact with these enterocytes.
what are the products of carbohydrate digestion? what happens to them?
• Thus, the final products of carbohydrate digestion are all monosaccharides.
They are all water soluble and are absorbed immediately into the portal blood.
• Glucose represents more than 80% of the final products of carbohydrate digestion, and galactose and fructose each seldom more than 10%.
where are peptidases located?
- The brush border consists of hundreds of microvilli projecting from the surface of each cell.
- In the membrane of each of these microvilli are multiple peptidases that protrude through the membranes to the exterior, where they come in contact with the intestinal fluids.
which two types of peptidase enzymes are especially important? what happens to the products? where are other enzymes?
- aminopolypeptidase
- dipeptidases
• They split large polypeptides into tripeptides and dipeptides and a few into amino acids.
• The breakdown products of polypeptides are transported through the microvillar membrane to the interior of the enterocyte.
• There are more specific peptidases inside the enterocyte.
• Once the peptides have been broken down into amino acids, they enter the blood from the basolateral membrane of the enterocyte.
where does some fat digestion occur?
- Some triglycerides are digested in the stomach by lingual lipase that is secreted by lingual glands in the mouth and swallowed with the saliva.
- This amounts for 10% of fat digestion.
- Fat digestion mainly occurs in the small intestine.
describe and explain the emulsification of fat
Emulsification of Fat by Bile Acids and Lecithin
• The first step in fat digestion is emulsification.
• This is the physical breakdown of fat globules into very small sizes so that the water-soluble digestive enzymes can act on the globule surfaces.
1. It begins by agitation in the stomach to mix the fat with the products of stomach digestion.
2. Then, most of the emulsification occurs in the duodenum under the influence of bile.
3. Bile doesn’t contain any digestive enzymes; however, it does contain a large quantity of bile salts as well as the phospholipid lecithin.
- The polar parts (the points where ionization occurs in water) of the bile salts and lecithin molecules are highly soluble in water, whereas most of the remaining portions of their molecules are highly soluble in fat.
o Therefore, the fat-soluble portions of these liver secretions dissolve in the surface layer of the fat globules, with the polar portions projecting. - The polar projections, in turn, are soluble in the surrounding watery fluids, which greatly decreases the interfacial tension of the fat and makes it soluble as well.
o When the interfacial tension of a globule of non-miscible fluid is low, this non-miscible fluid, on agitation, can be broken up into many very minute particles far more easily than it can when the interfacial tension is great.
o Consequently, a major function of the bile salts and lecithin, especially the lecithin, in the bile is to make the fat globules readily fragmentable by agitation with the water in the small bowel.
- As the fat globules are broken down (diameter is reduced) as a result of agitation in the small intestine, their surface area increases. Therefore, the emulsification process increases the surface area of the fat globules for the action of enzymes to follow.
describe the digestion of fat
The lipase enzymes are water-soluble compounds and can attack the fat globules only on their surfaces. The main enzyme to further break down fat globules is the pancreatic lipase enzyme.
o The triglycerides of the diet are split by pancreatic lipase into free fatty acids and 2-monoglycerides.
what is the role of bile salts in accelerating fat digestion?
• The hydrolysis of triglycerides results in accumulation of monoglycerides and free fatty acids in the vicinity of digesting fats, which block further digestion.
• Bile salts help prevent this.
They form a ‘micelle’ around the fat globule that is to be digested.
These develop because of the hydrophilic and hydrophobic nature of bile salts.
- Micelles also help transport the monoglycerides and free fatty acids to the brush borders of the intestinal epithelial cells.
- There the monoglycerides and free fatty acids are absorbed into the blood, but the bile salts themselves are released back into the chyme to be used again and again for this “ferrying” process.
- Emulsification of large fat droplets (increase surface area for action of lipase)
- Formation of mixed (contain mixture of monoglycerides, fatty acids, bile salts) micelles = stabilises products of TG hydrolysis (MG + FA) while they are ‘translocated’ to apical membrane from lumen
what stimulates pancreatic secretion (fats)?
- Triglycerides do not stimulate pancreatic secretion, but their hydrolytic products – monoglycerides and free fatty acids – do.
- The longer the chain of the fatty acid, the greater is the secretory response.
what are the different methods of absorption and what is absorbed my each method?
Simple diffusion – this is the main way in which lipids are absorbed
Carrier-mediated – amino acids, sugars and possibly lipids
- secondary active
- facilitated diffusion
Endocytosis - (receptor-mediated)
– vitamin B12 + intrinsic factor
-cholesterol
-small portion of absorption, although larger part when you are baby/younger
what are the different sites of absorption? and what absorbed there?
Mouth, oesophagus, stomach – limited diffusion
Duodenum and jejunum – this is the major site of nutrient and ion absorption
Ileum – vitamin B12 and bile salts & K+
(huge length of small intestine) (used for absorption if duodenum and jejunum don’t do good enough job)
Colon – some Na+ and H2O (+short chain fatty acids)
Rectum – limited diffusion
how is the small intestine adapted to being the prime site of absorption?
- Large absorptive surface area.
- Rich blood supply of blood vessels and lacteals (to drain lipids) found in the mucosal lining.
- Expansion of nutrient specific transport proteins.
o These belong to a family of transport proteins called “Solute Carrier (SLC) Transport Proteins”.
o Although, these transport proteins are found on the plasma membrane of the intestinal epithelial cells, they too can be found on the organelles inside the cell itself, thus leading to undefined side effects.
what are the three levels of the surface area of the small intestine?
- Folds of Kerckring
- Villi (+ crypts of Lieberkuhn)
- Microvilli
what does the small intestine absorb net amounts of? what does it secrete?
- The small intestine absorbs net amounts of water, Na+, Cl-, and K+.
- The small intestine secretes HCO3-.
with regards to absorption, what are the functional differences throughout the small intestine?
- Segmental heterogeneity
Different parts of the small intestine are involved in the absorption of different components of diet. - Crypt-villus/surface heterogeneity
Absorptive function is located in villous cells in the small intestine, whereas secretory processes reside in the crypt cells. - Cellular heterogeneity
Specific transport mechanisms are restricted to certain cells.
how are carbohydrates absorbed? what form? how?
• Essentially all the carbohydrates in the food are absorbed in the form of monosaccharides; only a small fraction are absorbed as disaccharides and almost none as larger carbohydrate compounds.
• There are three monosaccharides that are absorbed:
1. Glucose – most abundant monosaccharide absorbed (80%). This is because glucose is the final digestion product of carbohydrates.
2. Galactose
3. Fructose
• All monosaccharides are absorbed by an active transport process.
glucose absorption is dependent on what? why?
- Glucose absorption is dependent on Na+ ion absorption.
* Glucose absorption occurs in a cotransport mode with active transport of sodium.
describe the absorption of glucose from lumen to blood
- what transporters
- type of transport
• There are two stages in the transport of sodium through the intestinal membrane that cause absorption of glucose:
1. Active transport of sodium ions through the basolateral membranes of the intestinal epithelial cells into the blood, thereby depleting sodium inside the epithelial cells.
2. Decrease of sodium inside the cells causes absorption of sodium ions from the intestinal lumen across the apical membrane of the epithelial cells to the cell interiors by a process of facilitated diffusion.
2Na+ ions bind to a sodium-glucose transporter protein.
This causes absorption of glucose.
The low concentration of sodium inside the cell literally “drags” sodium to the interior of the cell and along with it the glucose at the same time.
Once inside the epithelial cell, other transport proteins and enzymes cause facilitated diffusion of the glucose through the cell’s basolateral membrane into the paracellular space and from there into the blood.
- Na+/K+-ATPase pump – basolateral membrane
- Na+-dependent co-transporter SGLT1 (sodium-glucose transporter 1)(secondary active into cell) (2Na+ and 1glc (glucose)) (works for glucose and galactose – they’re both hexose sugars)
- GLUT2 (facilitated diffusion out of basolateral membrane) (glucose transporter) (fructose can also move out of the cell via this)
Secondary active transport = against a concentration gradient – energy derived from Na+ gradient created by Na+ pump (Na+ pump = primary active transport)
how is galactose transported?
by the same mechanism as glucose.
how does fructose absorption take place?
- what happens to it
- what is rate
- what transporter
Fructose absorption does not occur by the sodium co-transport mechanism. Instead, fructose is transported by facilitated diffusion all the way through the intestinal epithelium but not coupled with sodium transport.
Much of the fructose, on entering the cell, becomes phosphorylated, then converted to glucose, and finally transported in the form of glucose the rest of the way into the blood.
Because fructose is not co-transported with sodium, its overall rate of transport is only about one half that of glucose or galactose.
- GLUT5 (facilitated diffusion into cell) (fructose = pentose sugar)
- GLUT2 (facilitated diffusion out of basolateral membrane) (glucose transporter) (fructose can also move out of the cell via this)
describe the absorption of fats
- The bile micelles, which develop during digestion of fats, are soluble in chyme because of their size and their highly charged exterior.
- In this form, the monoglycerides and free fatty acids are carried to the surfaces of the microvilli of the intestinal cell brush border and then penetrate into the recesses among the moving, agitating microvilli.
- Here, both the monoglycerides and fatty acids diffuse immediately out of the micelles and into the interior of the epithelial cells, which is possible because the lipids are also soluble in the epithelial cell membrane.
- This leaves the bile micelles still in the chyme, where they function again and again to help absorb still more monoglycerides and fatty acids – a “ferrying” function.
- After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the cell’s smooth endoplasmic reticulum; here, they are mainly used to form new triglycerides that are subsequently released in the form of chylomicrons.
- These chylomicrons are exocytosed through the base of the epithelial cell, and are transported in the lymphatic system to the liver.
FAT ABSORPTION (A DEVELOPING STORY)
i. Simple diffusion of FA – limited with few FFAs in undissociated state (pKa about 4.9)
ii. FFA transporters – FAT plus CD36 + others? (SCFA transporter in colon)
iii. MG transport – evidence for carrier-mediated mechanisms (no detail)
MG & FA ABSORPTION & TG RE-SYNTHESIS
- FA & MG are absorbed (in some way) … (lets just say simple diffusion)
THEN:
- TG re-synthesised in ER, packaged in chylomicrons
- Exocytosis of chylomicrons
- Chylomicrons transported in lymphatic system to liver
describe and explain the direct absorption of fatty acids into the portal blood
- Small quantities of short- and medium-chain fatty acids are absorbed directly into the portal blood rather than being converted into triglycerides and absorbed by way of the lymphatics.
- The cause of this difference between short- and long-chain fatty acid absorption is that the short-chain fatty acids are more water-soluble and mostly are not reconverted into triglycerides by the endoplasmic reticulum.
- This allows direct diffusion of these short-chain fatty acids from the intestinal epithelial cells directly into the capillary blood of the intestinal villi.
absorption of proteins
- in what form are they absorbed
- how
- how are some others absorbed
- how many different types of transporting proteins
• Most proteins, after digestion, are absorbed through the luminal membranes of the intestinal epithelial cells in the form of dipeptides, tripeptides, and a few free amino acids.
• The energy for most of this transport is supplied by a sodium co-transport mechanism in the same way that sodium co-transport of glucose occurs:
Most peptide or amino acid molecules bind in the cell’s microvillus membrane with a specific transport protein that requires sodium binding before transport can occur.
After binding, the sodium ion then moves down its electrochemical gradient to the interior of the cell and pulls the amino acid or peptide along with it.
This is called co-transport (or secondary active transport) of the amino acids and peptides.
• A few amino acids do not require this sodium co-transport mechanism but instead are transported by special membrane transport proteins in the same way that fructose is transported, by facilitated diffusion.
• At least five types of transport proteins for transporting amino acids and peptides have been found in the luminal membranes of intestinal epithelial cells. This multiplicity of transport proteins is required because of the diverse binding properties of different amino acids and peptides.
AMINO ACIDS ABSORPTION
- 20 dietary amino acids with a range of physical properties (e.g. neutral, acidic, basic, imino, etc.)
- 50% absorbed by PepT1 as di- & tri-peptides (hydrolysed to a.a. in enterocyte – released from the basolateral membrane of cell as amino acids)
- Other 50% by specific transporters
- XAG- -> anionic (aspartate, glutamate)
- B0 -> neutral a.a.
- b0+ -> cationic & cystine
- PAT1 -> proline
AMINO ACIDS – SECONDARY ACTIVE TRANSPORT
PepT1 – peptides, H+ (always a concentration gradient of H+ into cell) - cotransport
B^0 – Na+, alanine – cotransport
XAG- - 2Na+, glutamate-, H+, K+ (goes out) – cotransport
absorption of water - how? how much absorbed and where? what not transported by?
- Water is transported through the intestinal membrane entirely by diffusion (osmosis).
- This is due to an osmotic gradient that is created as a result of absorption of ions in the paracellular spaces, and consequently into the blood.
- Conversely, water can also be transported in the opposite direction—from plasma into the chyme.
- Much of the osmosis occurs through the tight junctions between the apical borders of the epithelial cells, but much also occurs through the cells themselves.
ABSORPTION OF H2O
- H2O moves down osmotic gradient
- Osmotic gradient created (mainly) by absorption of nutrients
- 8.4 l absorbed in total per day (due to water consumed as well as all the secretions produced)
-6.5 l absorbed in small intestine
-whereas only 1.9 l absorbed in colon (fairly minor role contrary to what people believe)
Route for H2O: (not quite sure)
- Via junctional complexes between cells
- Via SGLT1 & a.a. transporters
- NOT aquaporin water channels (not expressed in small or large intestine tissues in any great number)
what is the mechanism for sodium absorption? what type of absorption?
- Sodium ions (Na+) are actively transported from inside the epithelial cells through the basal and side walls of these cells into paracellular spaces.
- This occurs due to the Na+/K+ ATPase pump mainly.
- Part of the sodium is absorbed along with chloride ions - the negatively charged chloride ions are mainly passively “dragged” by the positive electrical charges of the sodium ions.
- Active transport of sodium through the basolateral membranes of the cell reduces the sodium concentration inside the cell to a low value (50 mEq/L).
- Because the sodium concentration in the chyme is normally about 142 mEq/L (that is, about equal to that in plasma), sodium moves down this steep electrochemical gradient from the chyme through the brush border of the epithelial cell into the epithelial cell cytoplasm.
- This provides still more sodium ions to be transported by the epithelial cells into the paracellular spaces.
‘ACTIVE’ TRANSPORT OF NA+ (AND Cl-)
- Na-H exchanger (duodenum, jejunum)
- Na/glucose or Na/amino acid cotransporters (jejunum, ileum)
- Parallel Na-H and Cl-HCO3 exchangers (ileum, proximal colon)
- Epithelial Na+ channel (distal colon)
- Diets don’t contain a lot of sodium, so we’ll evolved to have a good absorption system of sodium so that we conserve it in our body – if you have a lot of sodium in your diet, then this can be contributory to hypertension
what is the effect of aldosterone on sodium absorption?
Aldosterone Greatly Enhances Sodium Absorption
• When a person becomes dehydrated, large amounts of aldosterone almost always are secreted by the cortices of the adrenal glands.
• Within 1 to 3 hours this aldosterone causes increased activation of the enzyme and transport mechanisms for all aspects of sodium absorption by the intestinal epithelium.
• And the increased sodium absorption in turn causes secondary increases in absorption of chloride ions, water (thereby overcoming the dehydration), and some other substances.
• This effect of aldosterone is especially important in the colon because it allows virtually no loss of sodium chloride in the faeces and also little water loss.
absorption of chloride ions
- where
- how
Absorption of Chloride Ions in the Duodenum and Jejunum
• In the upper part of the small intestine, chloride ion (Cl-) absorption is rapid and occurs mainly by diffusion.
• Absorption of sodium ions through the epithelium creates electronegativity in the chyme and electropositivity in the paracellular spaces between the epithelial cells.
• Then chloride ions move along this electrical gradient to “follow” the sodium ions.
absorption of bicarbonate ions
- where
- why
- how
Absorption of Bicarbonate Ions in the Duodenum and Jejunum
• Often large quantities of bicarbonate ions must be reabsorbed from the upper small intestine because large amounts of bicarbonate ions have been secreted into the duodenum in both pancreatic secretion and bile.
• The bicarbonate ion is absorbed in an indirect way as follows:
o When sodium ions are absorbed, moderate amounts of hydrogen ions are secreted into the lumen of the gut in exchange for some of the sodium.
o These hydrogen ions in turn combine with the bicarbonate ions to form carbonic acid (H2CO3), which then dissociates to form water and carbon dioxide.
The water remains as part of the chyme in the intestines, but the carbon dioxide is readily absorbed into the blood and subsequently expired through the lungs.
Thus, this is so-called “active absorption of bicarbonate ions”.
- HCO3- no active absorption in SI or LI
- Faces [K+] = 90 mM; [HCO3-] = 30 mM
how much is 1 unit of alcohol?
10ml or 8g pure ethanol.
where is alcohol absorbed? where transported to?
• Alcohol is absorbed from the upper small intestine via the portal vein and is then transported to the liver.
- also absorbed in the stomach
where and how is alcohol metabolised?
• Some alcohol is metabolized in the stomach by alcohol dehydrogenase.
Females have a lack of this enzyme, therefore, their recommended safe limit is less than that of men.
• The rest of the alcohol is metabolized in the liver:
Alcohol is converted to acetaldehyde and excreted by conversion to carbon dioxide in citric acid cycle.
The enzyme cytochrome p4502E1 is involved in the metabolism of alcohol in the liver.
- I think some is metabolised in the stomach because some ADH is found there (first pass metabolism) but most in liver
- ADH is found mostly in the liver and lining of stomach (but highest concentration in the liver)
- about 20% of alcohol absorbed in the stomach and 80% in the small intestine
what is the rate of metabolism of alcohol?
varies but is usually at a rate of 1 unit per hour.
what are the effects of alcohol?
- Alcohol has a stimulant effect at low levels.
- However, chronic use of alcohol (moderate to severe doses) has depressant effects on the CNS, mainly the depression of cardiovascular and respiratory centres in the brainstem.
• At low doses, alcohol has a protective effect against atheromas.
- Alcohol does not protect from CVD except in women over 55- up to 5 units per week
what happens in acute alcohol poisoning?
o Confusion, Loss of coordination o Vomiting (this is a good sign as the person is trying to eliminate the toxins from their body, however, this can lead to complications like aspiration). o Seizures, Irregular or slow breathing (less than eight breaths a minute), Blue-tinged or pale skin (due to low oxyhaemoglobin), Low body temperature (hypothermia), Stupor (being conscious but unresponsive), Unconsciousness (passing out)
how can alcohol affect different parts of the GI tract? what does it cause?
Mouth/ Upper GI tract
o Increased incidence of cancers of upper GI tract / aerodigestive tract
o Especially tongue, buccal mucosa, pharynx, upper oesophagus
o Associated particularly with spirit use
o Possible a co-factor with cigarette smoking
Oesophagus
o Carcinoma of oesophagus, especially squamous carcinoma
o Oesophageal varices (dilation of veins, subject to rupture), associated with chronic liver disease
Stomach
o Acute gastritis
o Acute ulceration
o Chronic peptic ulceration
o Portal gastropathy
Pancreas
o Acute pancreatitis
o Chronic pancreatitis
Liver
o Alcohol liver disease
Acute fatty change (early) - reversible
Alcoholic hepatitis - reversible
Hepatic fibrosis - reversible
Cirrhosis (severe) – irreversible
Hepatocellular carcinoma
what does a normal liver do?
- Protein synthesis (e.g. albumin 35-50g/L, clotting factors)
- Glycogen storage
- Deamination of polypeptides
- Detoxification of xenobiotics, hormones, ingested drugs
- Bilirubin metabolism
- Coagulation factor synthesis
