Flashcards in Physiology of digestion and absorption Deck (90):
What is the major site for digestion and absorption?
The small intestine
How big is the small intestine?
Approx 6m long and 3.5 cm wide
Duodenum: approx 25cm
jejunum: approx 2.5 m
ileum: approx 3m
What does the small intestine receive, and where does it receive it from?
Chyme from the stomach
Pancreatic juices from the pancreas
Bile from the gallbladder
Which hormones are secreted into the bloodstream by the small intestine?
Name the hormone, the part of the intestine it is secreted by, and the type of cell which secretes it.
Gastrin- from G cells in the duodenum
Cholecystokinin (CCK) from I cells in the duodenum and jejunum.
Secretin- from S cells of the duodenum
Motilin- from M cells of the duodenum and jejunum
Glucose-dependent insulinotropic peptide- from K cells in the duodenum and jejunum
Glucagon like peptide 1- L cells in the small and large intestine.
What do the hormones secreted by the small intestine all act on?
G protein coupled receptors.
What is succus entericus?
How much is secreted per day?
About 2 litres
Describe the control mechanisms of the secretion of intestinal juice
Parasympathetic nerve activity
Sympathetic nerve activity
What does intestinal juice contain?
Mucous from goblet cells- for protection and lubrication
Aqueous salt (mostly from the crypts)- for enzymatic digestion
No digestive enzymes
What are the two processes which occur in the mixing and propulsion of chyme?
Segmentation (mixing) and peristalsis (propulsion)
Describe what happens in the mixing of chyme.
This is segmentation.
Pacemaker cells in the small intestine cause a BER which is continuous. Distension by entering chyme causes the BER to reach threshold, which activates segmentation.
Segmentation in the empy ileum is triggered by gastrin from the stomach- this is the gastro-ileal reflex.
Segmentation is alternating contraction and relaxation of segments of circular smooth muscle. The chopping which results moves the chyme back and forth.
The duodenum has frequent segmentation contractions, and the ileum has fewer.
The movement is slow (take about 3-5 hours) to allow absorption to occur.
Describe what happens in the propulsion of chyme.
This is peristalsis.
Two activities which occur in the interdigestive, or fasting state.
1. A few localised contractions
2. The migrating motor complex (MMC)
Occurs between meals every 90-120 minutes
It is a strong peristaltic contraction passing the length of the small intestine- from the stomach to the ileo-caecal valve.
It clears the small intestine of undigested debris, mucous and sloughed epithelial cells between meals (housekeeper function).
What increases and decreases the strength of segmentation?
Parasympathetic stimulation enhances the strength of segmentation and sympathetic stimulation decreases the strength of segmentation.
What inhibits and triggers the migrating motor complex?
It is inhibited by feeding, vagal activity, gastrin and CCK.
It is triggered by motilin.
What are the pancreatic endocrine and exocrine secretions?
What is the collective name for the pancreatic exocrine secretions which go to the duodenum?
Endocrine: Insulin and glucagon
Exocrine: digestive enzymes secreted by acinar cells, aqueous sodium bicarbonate secreted by duct cells. These are secreted to the duodenum collectively as pancreatic juice.
How are the enzymes stored in the pancreas?
They are stored in acinar cells, in zymogen (proenzyme) granules.
Name the proteases secreted by the acinar cells.
What types of enzymes are secreted by acinar cells?
Proteases, amylases and lipases
What amylase is secreted by the pancreas?
What lipase is secreted by the pancreas?
Are the amylases and lipases secreted by the pancreas proenzymes or active enzymes?
They are active enzymes.
How and when are the proteases secreted from the pancreas activated?
What are they activated to?
They are activated in the duodenum, by the action of enterokinase from mucosal cells.
Trypsinogen becomes trypsin, which can then go on to also activate the other inactive proteases.
Chymotrypsinogen becomes chymotrypsin
Procarboxypeptidase becomes carboxypeptidase (A and B).
What is the function of the bicarbonate released from the duct cells in the pancreas into the duodenum?
It neutralises the chyme from the stomach.
This provides the optimum pH for pancreatic enzyme function, and protects the mucosa from erosion by acid.
Describe how fluid is secreted from duct cells in the pancreas
Carbonic acid is formed from carbon dioxide and water, under the action of carbonic anhydrase.
Carbonic acid then dissociates into bicarbonate and a proton.
The proton can be exported through the basal lateral membrane via: a sodium/hydrogen exchanger, or a potassium/hydrogen ATPase.
On the apical surface of the cell, bicarbonate exits via a chloride/bicarbonate antiporter.
The chloride is recycled via the CFTR chloride channel.
Therefore, in patients with CF with a mutated CFTR channel, they have reduced fluid secretion since they have less chloride exiting the cell.
What are the three phases of pancreatic secretion?
Cephalic, gastric and intestinal.
Describe the cephalic phase of pancreatic secretion.
This is mediated by vagal stimulation of mainly the acinar cells.
This contributes to 20% of the total pancreatic secretion.
Describe the gastric phase of pancreatic secretion.
Gastric distension evokes a vagovagal reflex, resulting in parasympathetic stimulation of acinar and duct cells. The stomach signals to the brainstem, which then signals to the pancres.
This makes up 5-10% of the total secretion.
Describe the intestinal phase of pancreatic secretion.
The two stimuli here are the present of acid in the duodenum and the presence of fat in the duodenum.
The presence of acid in the duodenum causes an increase in Secretin release from S cells, which is carried by the blood to the pancreatic duct cells and causes an increased secretion of aqueous sodium bicarbonate into the duodenum. This then neutralises the acid in the duodenum.
Fat and protein in the duodenum evokes an increased release of CCK from I cells in the duodenum. This is carried in the blood to the pancreatic acinar cells and causes increased release of digestive enzymes into the duodenum. These digest the protein and fat in the duodenum.
What does the biliary system comprise of?
The liver, the gallbladder and associated ducts
Where is bile synthesised?
By hepatocytes in the liver
Where does the bile go after it has been formed?
It is secreted into hepatic ducts, collects in the common hepatic duct, then passes into the common bile duct. In between meals it does not pass into the duodenum because the sphincter of oddi is tightly closed. Instead it is stored in the gallbladder.
How much bile is produced per day?
0.6 litres to 1.2 litres
What happens to bile during a meal?
It spurts into the duodenum via the cystic and common bile ducts.
This is because chyme in the duodenum stimulates the gall bladder to contract, and the sphincter of oddi opens.
Which secretions does bile consist of?
Where do these secretions mix?
Secretions of bile duct cells and secretions of hepatocytes.
These mix in the ducts.
What food group does bile aid in the digestion and absorption of?
Describe the effect of acid in the duodenum on pancreatic secretions, bile secretion and the gastric emptying and secretions.
Acid from chyme in the duodenum causes an increase in secretin released from S cells. The secretin is carried by the blood to:
a) the pancreatic duct cells, which secrete more aqueous sodium bicarbonate, which is secreted into the duodenum and neutralises the acid.
b) the hepatocytes and duct cells, which secrete more sodium bicarbonate rich bile.
c) the stomach- causes decreased gastric secretions and decreased gastric emptying.
Describe the effect of protein and fat in the duodenal lumen on pancreatic secretions, bile secretion and gastric emptying and secretion.
Fat and protein in the duodenal lumen causes increased secretion of cholecystokinin which is released from I cells and is carried by the blood to:
a) the pancreatic acinar cells, which secrete more digestive enzymes into the duodenum, which then digest the protein and fat there.
b) The gall bladder and the sphincter of oddi: there is contraction of the gallbladder and relaxation of the sphincter of oddi to cause a spurt of bile into the duodenum.
c) The stomach, to cause a decrease in gastric secretion and a decrease in gastric emptying.
What makes up starch?
Amylose (straight chain polymer of glucose) and amylopectin (branched polymer of glucose).
What makes up 46-60% of the carbohydrate we ingest?
Which carbohydrate is indigestable to human?
What is its function in humans?
What is glycogen?
A branched polymer of glucose
What makes up most of the lipids that we ingest?
Name endogenous sources of protein.
Digestive enzymes and dead cells from the GI tract.
Where is carbohydrate digested?
Name the enzymes which digest it at each location.
In the mouth by salivary alpha-amylase
In the stomach- digestion continues with salivary alpha-amylase which is now within the bolus
In the duodenum- Pancreatic alpha-amylase which is secreted by the pancreas and free in the duodenal lumen
Oligosaccharidases which are integral to the brush border membrane of enterocytes. These include: isomaltase, sucrase, lactase and maltase.
What form of carbohydrate can the small intestine absorb?
It can only absorb carbohydrate monomers.
E.g. glucose, fructose and galactose.
Can the large intestine absorb any carbohydrate monomers?
What kind of enzyme is amylase?
What linkages can it hydrolyse?
Amylase is an endoenzyme.
It can break internal alpha-1,4-glycosidic linkages, but will not attack terminal linkages.
It can also not hydrolyse alpha-1,6-glycosidic linkages as are found in branches of starch or glycogen, or beta-1,4-linkages as found in cellulose.
What are the products of the action of amylase?
Amylase can produce Maltose (2 glucose), maltotriose (3 glucose) and isomaltose (2 glucose with alpha-1,6-glycosidic linkages).
What does maltase do?
It cleaves alpha-1,4-glycosidic bonds.
It acts on maltose and maltotriose to produce glucose monomers.
What does isomaltase do?
It cleaves alpha-1,6-glycosidic bonds.
It hydrolyses isomaltose to give 2 glucose monomers.
What is sucrose?
This is a glucose and a fructose molecule bound together in a an alpha-1,2 bond.
What does sucrase do?
It cleaves the alpha-1,2 bond in sucrose to produce a glucose monomer and a fructose monomer.
What is lactose?
Glucose and galactose joined in a beta-1,4 bond.
What does lactose do?
It cleaves the beta-1,4 bond in lactose to produce a glucose monomer and a galactose monomer.
What makes some people "lactose intolerant"?
They lack an allele which encourages the persistence of the allele which codes for lactase. They therefore lack lactase and cannot digest lactose.
Why can carbohydrate monomers not diffuse across membranes?
They are polar.
What mechanism allows glucose and galactose to be absorbed in the small intestine?
Secondary active transport
Describe how glucose and galactose are pumped into an enterocyte from the lumen of the duodenum or jejunum.
They are pumped into the cell by secondary active transport, via the SGLT1 transporter (i.e. sodium glucose cotransporter 1).
A Sodium potassium ATPase on the basal lateral membrane of the enterocyte maintains the sodium gradient (i.e. there is a maintained lower concentration of sodium inside the cell than outside the cell). Therefore the passage of 2 sodium ions into the cell down its electrochemical gradient via the SGLT1 provides the energy to pump the glucose or galactose molecule into the cell.
How do glucose and galactose enter the bloodstream from the enterocyte?
By facilitated diffusion via a GLUT 2 transporter.
How does fructose enter the enterocyte from the lumen of the small intestine?
Facilitated diffusion via the GLUT 5 transporter.
How does fructose enter the bloodstream from the enterocyte?
Facilitated diffusion, by the GLUT 2 transporter.
What moves into the cell along with the carbohydrate monomers and sodium?
Where is protein digested?
In the stomach and in the duodenum
Describe protein digestion in the stomach
HCl denatures the protein by unwinding its secondary structure and exposing its peptide linkages to pepsin.
Pepsin then cleaves the protein into peptides.
Describe protein digestion in the duodenum.
Pancreatic enzymes (e.g. trypsin and chymotrypsin) are endoenzymes and split peptide bonds between amino acids in the complex polypeptide. However they cannot attack the terminal bonds.
They have exposed more amino and carboxy groups and created small peptide fractions.
Brush border enzymes such as carboxypeptidase, aminopeptidase or dipeptidase cleave amino acids at the end of the molecules, or hydrolyse dipeptides. Carboxypeptidase cleaves bonds present at the carboxy terminus, aminopeptidase cleaves bonds present at the amino terminus and dipeptidase hydrolyses dipeptides.
What are the final products of digestion?
In infancy some intact proteins can be absorbed by endocytosis.
How are amino acids absorbed by the enterocytes?
Some hydrophobic amino acids can pass into the enterocyte by passive diffusion
Others are pumped in by secondary active transport (5 Na dependent transporters and 2 Na independent transporters).
How are di and tripeptides absorbed into enterocytes?
NaK pump on the basal lateral membrane creates a sodium electrochemical gradient which encourages sodium flow into the cell. Therefore the energy from sodium flowing into the cell can be used to pump H+ ions out, and create an electrochemical gradient which favours H+ flow into the cell via the H+/peptide cotransporter. The energy from H+ ions flowing into the cell can be used to pump peptides into the cell.
What happens to di and tripeptides once they have moved into the enterocyte?
They are cleaved to their amino acid subunits
How do amino acids cross the basolateral border of the enterocyte?
Where are lipids digested?
Mouth, stomach and small intestine
What carries out lipid digestion in the mouth?
Lingual lipase, and has little effect.
What carries out lipid digestion in the stomach?
gastric lipase, and has a modest effect.
Describe lipid digestion in the small intestine.
There is emulsification by bile
Pancreatic lipase splits lipids into fatty acids and monoglyceride.
Describe digestion of TAG in the stomach.
Heat and movements in the stomach mix food with gastric lipase which begins digestion and forms an emulsion.
Hydrolysis is initially slow due to a largely separate aqueous/lipid interface.
As hydrolysis proceeds, its rate increases as the fatty acids produced act as surfactants, breaking up lipid globules aiding emulsification.
Gastric lipase hydrolyses one of the ester bonds in TAG to form DAG and a free fatty acid.
These are ejected from the stomach. To be absorbed, need a monoglyceride and free fatty acids so there must be further digestion in the small intestine.
Describe TAG digestion in the duodenum.
Bile from the gallbladder breaks up lipid droplets into even smaller ones.
Pancreatic lipase is the main lipid digestive enzyme and digests it further.
How do bile salts aid digestion of fats?
They act as detergents to emulsify large lipid dropets to smaller droplets. Bile salts are amphipathic. They have a hydrophobic steroid core which dissolves in the fat globule, and polar residues which project from the surface of the droplet, preventing it from rejoining with other droplets. This increases the surface area available for digestion by pancreatic lipase.
What does a failure to secrete bile salts result in?
Lipid malabsorption which leads to steatorrhoea
Secondary vitamin deficiency due to failure to absorb lipid vitamins.
What does colipase do?
The coating of the lipid droplet with the bile salts impairs the accessibility of the water soluble lipase to its lipid substrate. To overcome this problem, the pancreas secretes a protein called colipase which is ampipathic and lodges on the lipid droplet surface. Colipase binds the lipase enzyme, holding it on the surface of the lipid droplet.
Which ester bonds in TAG does pancreatic lipase attack?
the first and the third, therefore it produces 2 free fatty acids and 2-monoglyceride.
Where are the products of lipid digestion stored in the small intestine?
What do these structures contain?
They are stored in mixed micelles.
Micelles contain monoglycerides, fatty acid, bile salts, phospholipids and cholesterol.
How are free fatty acids and monoglycerides transferred from the micelle to the enterocyte?
They pass into the enterocyte from the micelle by passive diffusion.
What happens to short and medium chain fatty acids in the enterocyte?
Short chain <6 carbons
Medium chain 8- 12 carbons
These diffuse through the basolateral membrane and enter the villus capillaries.
What happens to long chain fatty acids in the enterocyte?
Long chain > 12 carbons
They are resynthesised to TAG with monoglycerides in the endoplasmic reticulum and are packaged into chylomicrons.
What happens to chylomicrons once they have been formed in the endoplasmic reticulum of enterocytes?
These are exported by exocytosis from the basolateral membrane and enter teh central lacteal of the villus, are transported in the lymph to the subclavian vein via the thoracic duct.
What happens to the triglycerides in the chylomicrons?
It is metabolised in the capillaries (particularly in muscle and adipose tissue) by lipoprotein lipase present on endothelial cells.
The free fatty acids and glycerol released initially bind to albumin and then are taken up by tissues.
What is the remainder of the chylomicron called once the TAG has been removed?
What is in it?
What happens to it?
It is called a chylomicron remnant.
It is enriched in phospholipid and cholesterol.
The chylomicron remnant undergoes endocytosis by hepatocytes. Cholesterol is released, and is either stored, secreted unaltered in bile, or oxidised to bile salts.
How is cholesterol absorbed by enterocytes?
By endocytosis in clathrin coated pits by NPC1L1 protein.
The protein inserts into the membrane, picks up cholesterol from the lumen, brings it into the cytoplasm by endocytosis, cholesterol is packaged into chylomicrons, then it returns to the membrane to repeat the process.
What controls the expression of NPC1L1 in the enterocyte?
The amount of cholesterol in the enterocyte