Physiology of Digestion and absorption Flashcards
what is the major site for digestion and absoption
the small intestine
what are the three parts of the small intetsine
duodenum, jejunum, ileum
what does the small intestine recieve
chyme from stomach, pancreatic juice from the pancreas, bile from the gall bladder
what does the small intestine move its contents to
the large intestine via the ileocaecal valve
what increases the surface area of the small intestine
circular folds, villi, microvilli
what peptide hormones does the small intestine secrete
gastrin, cholecystokinin (CCK), secretin, motilin, glucagon like insulintropic peptise (GIP a.k.a gastric inhibtory peptide), glucagon like peptide 1 (GLP-1), ghrelin
what do all peptide hormones secreted by the small intestine work on
G-protein coupled receptors
what controls the secretions of the small intestine
Distension/irritation, gastrin, CCK, secretin, parasympathetic nerve activity (all enhance), sympathetic nerve activity (decreases)
what does intestine juice contain
mucus (protection and lubrication- goblet cells)
aqueous salt (for enzymatic digestion)
NO digestive enzymes
what initiates segmentation in the small intestine
small intestine pacemaker cells causing the BER which is continuous. At threshold activates segmentation which in the duodenum is primarily due to distension by entering chyme
what is segmentation in the empty ileum triggered by
gastrin from the stomach (gastroileal reflex)
why is the movement of chyme slow (3-5 hrs)
allows time for absorption
what is the strength of segmentation affect by
enhanced by parasympathetic and decreased by sympathetic activity
what is the migrating motor complex (MMC)
strong peristaltic contraction passing length of the intestine (stomach to ileocaecal valve)
clears small intestine of debris, mucus and sloughed epithelial cells between meals – ‘housekeeper function’
what is the MMC inhibited by
feeding and vagal activity, gastrin and CCK
what trigger the MMC
motilin
when does the MMC happen
between meals every 90 to 120 min
what are the endocrine secretions of the pancreas
insulin and glucagon (secreted to blood)
what is the difference between endocrine and exocrine
Endocrine glands release chemical substances directly into the bloodstream or tissues of the body
Exocrine glands release chemical substances through ducts to outside the body or onto another surface within the body
what are the exocrine secretions of the pancreas
digestive enzymes, aqueous NaHCO1- solution (secreted to the duodenum collectively as pancreatic juice)
where do pancreatic duct cells drain into
the duodenum (1-2 litres of alkaline fluid a day)
what is the role of the alkaline fluid secreted from the pancreatic duct cells
neutralises chyme entering the duodenum
- provides optimum pH for pancreatic enzyme function
- protects the mucosa from erosion by acid
what do patients with CF have
reduced fluid secretion for the pancreatic duct cells
what ability do pancreatic enzymes have
to digest food in absence of all other enzymes
give example of pancreatic enzymes secreted within the pancreatic juice
inside brackets name for active state- outside inactive
no brackets means active when secreted
(trypsin)ogen
(chymotrypsin)ogen
pro(carboxypeptidase A & B)
pancreatic amylase
pacreatic lipase
where are many pancreatic enzymes activated
in the duodenum
what are the three stages of pancreatic secretion
cephalic, gastric and intestinal
what is the cephalic stage of pancreatic stimulation mediated by
vagal stimulation of mainly acinar cells
what is the gastric stage of pancreatic stimulation mediated by
gastric distention evokes a vagovagal reflex resulting in parasympathetic stimulation of acinar and duct cells
what is the secretory pathway for the neutralisation of duodenal lumen
acid in duodenal lumen
increased release of secretin from S cells
secretin carried by blood to pancreatic duct cells
increased secretion of aqueous NaHCO3 solution into duodenal lumen
neutralisation
what is the secretory pathway of the digestion of fat and protein in the duodenal lumen
fat and protein in duodenal lumen
increased CCK release from I cells
CCK carried in blood to pancreatic acinar cells
increased secretion of digestive enzymes into duodenal lumen
digestion
what are the main constitutes of food
carbohydrates (starch, cellulose, glycogen, disaccharides)
lipids (triacylglycerols, phospholipids, cholesterol and cholesterol esters, free fatty acids, lipid vitamins)
proteins
define digestion
enzymatic conversion of complex dietary substances to a from that can be absorbed
what are the two types of digestion that occur in the small intestine
luminal and membrane digestion
what is luminal digestion mediated by
pancreatic enzymes secreted into the duodenum
what is membrane digestion mediated by
enzymes situated at the brush border of epithelial cells
describe absorption in digestion
the absorbable products of digestion are transferred across both the apical and basolateral membranes of enterocytes (absorptive cells of the intestinal epithelium)
what is assimilation
overall process of digestion and absorption
what must all dietary carbohydrate be converted into for absorption
monosaccarhides
what is the sequence of carbohydrate digestion (not including enzymes)
starch to oligosaccharides to monosaccharides to absorption
what is involved with intraluminal hydrolysis
starch converted to oligosaccharides (not absorbed)
what is involved in membrane digestion
oligosaccharides and lactose and sucrose from diet are converted into monosaccarhides, (+ glucose and frutose) from diet = absorption
where does membrane digestion happen
at brush border
what enzyme facilitates the conversion of starch to oligosaccharides
alpha- amylase
what enzyme facilitates the conversion of oligosaccharides to monosaccharides
oligosaccharidases (lactase, maltase)
give examples of oligosaccharides
maltose, alpha-limit dextrins, maltotriose (lactose and sucrose from diet)
give exmaples of monosaccharides
glucose, fructose, galactose
what is the role of amylase
is an endo enzyme - breaks down linear internal α-1,4 linkages but not terminal α-1,4 linkages. Hence, no production of glucose
what can alpha amylase not cleave
α-1,6 linkages at branch points (in amylopectin) or α-1,4 linkages adjacent to branch points
what are the products made by alpha amylase
linear glucose oligomers (maltotriose, maltose) and α-limit dextrins
what are olisacchardiases
integral membrane proteins with a catalytic domain that faces the lumen of the GI tract
what is the role of lactase
breaks down lactose to glucose and galactose
what do all oligosaccharidases do expect lactase
cleave the terminal alpha 1,4 linkages of maltose, maltriose and alpha-limit dextrins to yield glucose
what is sucrase specifically responsible for
hydrolysing sucrose to glucose and fructose
what is the only enzyme that can split up branches
isomaltase
what enzymes hydrolysis is rate limiting is assimilation
lactase
what causes lactose intolerance
the inability to adequately digest lactose- cause by lactase insufficiency
what can cause lactase intolerance
primary (lack of lactase persistence),
secondary (damage/ infection of small intestine),
congenital (rare autosomal recessive disease)
what is lactase persistence
Lactase activity is generally lost in mammals following weaning, but human populations exhibit a variable degree of lactase persistence
when does hypolactasia (lactase insufficiency) cause disturbance
when lactose containing food in comsumed and activity of remaining enzyme is overwhelmed, meaning lactose is delivered to the colon
what do the ileum colonic microflora produce when lactose is delivered to the colon
short chain fatty acids (can be absorbed), hydrogen, carbon dioxide, methane
what are the symptoms cause by by products made when lactose in the colon
bloating, abdominal pain, flatulence
what does undigested lactose cause
acidification of the colon, an increased osmotic load (loose stools and diarrhoea)
where does the absorption of the final products of carb digestion occur
duodenum and jejunum
what are the final products of carb digestion
glucose, galactose and fructose
how are the final products of carb digestion absorbed
two step process involving entry from the enterocytes via the apical and exit basolateral membranes.
Glucose and galactose are absorbed by secondary active transport mediated by SGLT1; fructose by facilitated diffusion mediated by GLUT5.
Exit for all monosaccharides is mediated by facilitated diffusion by GLUT2
what forms must proteins be in to be absorbed
must be digested to oligopeptides and amino acids for efficient absorption
how much on daily energy intake does protein assimilate to
10-15%
how is protein digested in the stomach
HCL begins to denature proteins, pepsin cleaves proteins into peptides
describe the pH of pepsin
optimum of 1.8 to 3.5, inactivated at alkaline pH
is pepsin essential for protein digestion
no
what type of enzyme is pepsin
endopeptidase
describe the enzyme active in protein digestion in the duodenum and how they get there
five pancreatic proteases are secreted as proenzymes from the exocrine pancreas and converted to active form in the duodenum. They function as either endopeptidases, or exopeptidases
what are the 5 pancreatic proteases
trypsin, chymotrypsin, elastase, procaroxypeptidase A and B
what is the ratio of converted oligopeptides and free amino acid from pacreatic protease protein digestion
70% oligopeptides
30% AA
where are additional proteases present
at the brush border and within the cytoplasm of the enterocyte
where are amino acids absorbed
at the brush border and basolateral membranes
how are di- tri- and tetra- peptides absorbed
at bush border
further hydrolysed to amino acids within the enterocyte
Na+-independent systems at the basolateral membrane (facilitated transport) takes into interstitium PepT1
when things are absorbed where do they go
from lumen, inter enterocyte, out to interstitium
what do peptidases at the brush border do
further hydrolyse oligopeptides to amino acids
how are amino acids absorbed
Amino acids are transported across the apical membrane via a variety of amino acid transporters, some of which are Na+-dependent and others Na+-independent
how are oligopeptides transported across the apical membrane
by the H+/oligopeptide co-transporter, PepT1
how are oligopeptides hydrolysed to amino acids within the enterocyte
by peptidases
how do amino acids exit the enterocyte
across the basolateral membrane by several, Na+-independent. transporters
what enzymes can proteins be digested by
luminal or brush border enzymes (digest protein to peptide and then to amino acid)
what is the path of the amino acids
apical membrane transporters with the enterocytes, then basolateral membrane transporters take them from enterocyte into the blood (or peptides can go through entracellular hydrolysis and go straight into the blood)
what are the luminal proteins
gastric and pancreatic proteases
who does as endopeptide do
breaks down amino acids from anywhere in chain, not just at terminal ends
how can the five pancreatic proteases function
as endopeptidases and exopeptidases (breakdown terminal ends)
why are there so many peptidases
as large diversity of peptide bonds, specialised enzymes needed to cleave different types of bonds
what are two exopepditases
aminopeptidases and carboxypeptidases
what is present at the brush border IMPORTANT
5 Na+ dependant co transporters that mediates movement against gradient, mediates uptake of neutral amino acids
2 Na+ independent co transporters that mediates uptake of cationic amino acids
what are the 5 mechanisms of amino acid transport in the basolateral membrane
3 medaite efflux from enterocytes into blood (Na+ independent)
2 mediate influx from blood into enterocyte and are Na+ dependent
how are di- tri- and tetra peptides moves across apical membrane IMPORTANT
via H+ dependent (c transport with a proton) mechanism PepT1 at brush border- further hydrolised within enterocyte
how soluble are lipids in water
insoluble or poorly soluble
what is the most important part of the GI tract for lipid digestion
small intestine
what stops droplets of lipids in an emulsion coagulating
by the addition of a amphiphillic coat
what are the phases of lipid digestion
mouth- lingual phase
stomach- gastric phase (gastric lipase)
small intestine- most important, emulsification of bile
what type of fatty acid cannot be absorbed by the liver
long chain
what does pancreatic lipase do
hydrolyses TAGs (triacytglycerols) to monoglyceride and free fatty acids
what is the main lipid digestive enzyme in in adults
pancreatic (TAG) lipases - in duodenum
describe the secretion of pancreatic (TAG) lipases
secreted from acinar cells of pancreas in response to CCK which also stimulates bile flow
what is the role of bile salts
secreted in bile, released into duodenum from the gall bladder in response to CCK act as detergents to emulsify large lipid droplets to small droplets- increase the surface area of lipase action
what does a failure to secrete bile result in
lipid malabsorption- steatorrhoea
secondary vitamin deficiency due to failure to absorb lipid vitamins (A, D, E and K)
how are bile salts amphipathic
as both hydrophilic (projects from surface of doplet) and hydrophobic (absorbs onto droplet)
what is the relationship of bile salts and pancreatic lipase
bile salts increase SA for attach by PL but block access to the lipid with the hydophobic core of the small droplets
how is the lipid bloackage by bile salts overcome
by colipase which binds to bile salts and lipase allowing access to tri and di glycerides
what is colipase
an amphipathic polypeptide secreted with lipase by the pancreas
digestion of triglyceride by pancreatic lipase produces what
2-monoglyceride and 2 free fatty acids
where are the final products of lipid digestion stored in and released from
mixed micelles
how do free fatty acids and monoglycerides enter the enterocytes
by passive diffusion/ transport proteins
where do short chain (<6 carbons) go after entering the enterocyte
exit through basolateral membrane and enter the villus capillaries
where do long chain fatty acids (>12 carbons) and monoglycerides go after entering the enterocyte
are resynthesized to triglycerides in the endoplasmic reticulum and are incorporated into chylomicrons
what happens to chylomicrons in the enterocytes
leaves via exocytosis into central lacteal-
carried in lymph vessels to systemic circulation via the thoracic duct
what happens to chylomicron triglyceride once it is distributed to tissues (particularly muscle ans adipose tissue)
metabolised in capillaries by lipoprotein lipase on endothelial cells - fatty acids and glycerol released which bind to albumen and are taken up by tissues
what happens to the chylomicron remnant- not metabolised
enriched with phospholipids and cholesterol then undergoes endocytosis by hepatocytes- cholesterol released to be stores, secreted in bile, oxidised to bile salts
how is cholesterol absorped
via NPC1L1 protein
what drug prevents cholestrol absorption by NPC1L1 and is used with statins in hypercholesterolaemia
ezetimibe
what regulates acitve Ca+ absorption
calcitriol and parathyroid hormone
how is calcium absorped
passive (paracellular) in small intestine
active (transcellular) in duodenum and upper jejunum
what converts Fe3+ to Fe2+
Vit c
what is the storage form of iron
ferratin
what negatively regulates the absorption of iron when levels in body are high
hepcidin- released from liver
what is needed to absorb vit B12
firstly binds to haptocorin, then released and binds to intrinsic factor which makes complex which is absorbed via endocytosis
what are the fat soluble vitamins
A,D,E and K
how are fat soluble vitamins absorbed
Incorporated into mixed micelles
Usually passively transported into enterocytes
Incorporated into chylomicrons, or VLDLs
Distributed by intestinal lymphatics
what are the water soluble vitamins
B (not B12), C, H
how are water soluble vitamins absorbed
Transport processes in the apical membrane are similar to those described for monosaccharides, amino acids and di- and tri-peptides
