Digestion and Absorption - Jacinto 2/25/16 Flashcards
overview of digestion and absorption in intestine
digestion: occurs in lumen and on membrane surface
- enzymes and transporters in brush border are often heaviily glycosylated so they wont be digested by luminal digestive enzymes
absorption: from lumen into blood and lymph
surface area amplification
levels on levels of folds in intestinal lumen (villi made of epithelial cells with microvilli)
- length of sm int ~ .33 m2
- fold of Kerkring, 3x
- villi, 10x
- microvilli, 20x
- total SAn~ 175 m2
intestinal villi structure
intestinal cells
- born in crypts
- mature/migrate to apical portion of microvilli
- total lifespan: 4-5 days
- superproliferative
villi interior: lacteals and capillaries
- capillaries for nutrient abs and oxygen delivery
- lacteals for lymph
transport of nutrients across enterocyte
types of transporters
enterocyte = int epithelial cell
1. passive: no energy, down conc gradient
2. primary active: ATP-ase, establishes concentration gradient for other transport
3. secondary active: symporters or antiporters that take multiple things across membrane, driven by an existing conc gradient
also as a means of transport to leave the cell
carbs in the diet
- plant starch: amylopectin, amylose
- dietary fiber: cellulose
- animal starch: glycogen
- disaccharides: sucrose, lactose
- monosaccharides: glucose, fructose
carb breakdown: amylases
starch/glycogen digested via breakdown of 1:4 linkages (linear) and 1:6 linkages (perpendicular) by amylases
- mouth: salivary amylase
- partially degrade carbs → generate disacchs, trisacchs, alpha-limit dextrin with 1:6 link
- once you get to stomach, amylase is deactivated
- intestine: duodenum/jejunum: pancreatic amylases go to work, break down into monosacchs
- most absorption happens in upper sm int
carb breakdown
luminal vs membrane digestion
luminal digestion
- salivary amylase, pancreatic amylase
- can digest polysacchs into disacchs (lactose, dextrins, maltotriose, maltose, trehalose, sucrose)
membrane digestion
- lots of disaccharidases which take dissachs and break down into glucose/galactose/fructose
abs of dietary carbs
lumen into enterocyte (apical side)
- fructose via GLUT5
- glucose/galactose via SGLT1
enterocyte into circulation (baslateral side)
- fructose/glucose/galactose via GLUT5
gradient for SGLT1 action maintained by Na/K ATPase
carb maldigestion
[lactose intolerance]
lactose intolerance: inability to break down dairy products (occurs on a spectrum)
- after infancy, enzyme needed to digest them (lactase) drops in production
- NOT AN INABILITY TO ABSORB; it’s an inability to digest the products in the first place
what happens to the lactose?
- in colon, bacteria use it as a source of nutrients, break it down and make H2 gas (pt feels bloated, gassy)
- bacterial fermentation produces short chain FAs
bacterial fermentation in lactose intolerance
why is it a good thing?
bacterial fermentation of lactose that makes it to the colon produces H2 gas as well as short chain FAs
- salvages calories from lactose that cant otherwise be gotten
- reduces water loss in feces
- combats int inflammation: FAs can support regulatory T cells in gut immune system
carb dig/abs abnormalities
1. genetic
- lactose intolerance
- glucose/galactose malabsorption : SGLT1 error
2. pancreatic insufficiency : issues with panc amylase
3. secondary cause (non-genetic)
- decreased abs surface area = reduction # of membrane enzymes
- parasitic infection
proteins in diet
- animals and plant sources
- endogenous proteins: recycling of proteins from digestive enzymes, dead epithelial cells
digestion of proteins
- no digestion in mouth
- digestion begins in stomach via pepsin → polypeptides + a.a.s
- pancreatic proteases [trypsin, chymotrypsin, elastase, carboxy-peptidase] → oligopeptides + a.a.s
- intestinal proteases [amino peptidases, di- and tripeptidases] → a.a.s
protein digestion
luminal vs membrane digestion
luminal digestion
- pepsin, pancreatic proteases
membrane digestion
- peptidases in brush border to break down large peptides
- carrier proteins that can move di/tripeptides in
enzymes involved in protein digestion
- stomach chief cells release pepsinogen (zymogen)
- pepsinogen activated → pepsin by stomach acidity
- pepsin isn’t particularly efficient at hydrolyzing polypeps - mostly recognizes a.a.s
- sm intestine enteropepsidase activates trypsinogen → trypsin
- trypsin then activates a bunch of proenzymes → [trypsin, chymotrypsin, elastase, carboxypeptidase A, carboxypeptidase B]
di- and tripeptides
once in cells, di- and tripeptides are further digested by cytoplasmic peptidases → a.a.s, which move into bloodstream
protein absorption
- passive transport
- [majority] Na-a.a. cotransport
* NHE can drive absorption by setting up gradient
absorption is efficient, but not as efficient as carbs
protein dig/abs abnormalities
- genetic
- enteropeptidase deletion (can’t activate trypsin)
- not the worst; autohydrolysis of trypsinogen is possible; survivable defect
- trypsinogen deletion
- amino aciduria (cystinuria, prolinuria)
- Hartnup’s disease: Trp transporter
- pancreatic insufficiency
- other
- decreased surface area
- surgery
- parasitic infection
nucleoprotein dig/abs
digestion
- pancreatic DNase, RNase
- polynt hydrolysis via brush border phosphodiesterases and nucleotidases
absorption
- nucleoside transporters
- uric acid excreted in urine
- sugar reabsorbed into circ
dig/abs of vitamins
- in most cases, protein to which the vitamin is bound is digested
- vitamin is released and absorbed by specific transporters in int (most in upper part of sm int)
-
exception: B12/cobalamin
- deficiency or malabs can lead to pernicious anemia
absorption of B12/cobalamin
B12/cobalamin-IntrinsicFactor binds to cubulin receptor in the ileum → endocytosis
- deficiency can be due to strict veg diet
- def can also be due to issues with dig/abs
- lack of IF
- pancreatic insufficiency
- intestinal disorders
the process
in stomach,
- food-bound B12 interacts with stomach acid, becomes unbound
- R protein/haptocorrin [formerly known as transcobalamine] binds to B12 to protect it from acidity of stomach
- IF produced
in sm intestine
- R protein gets digested, B12 on its own again
- IF binds newly single B12
in ileum
- you find IF-Cbl receptors on enterocytes
ways B12 abs could be compromised
- lose ileum
- not secreting IF
- defects in R protein [if you cant get your pancreatic enzymes to get R protein off]
Roux en Y surgery
gastric bypass [obesity, diabetes]
- stomach stapled (cuts down on ingestion - can only tolerate small portions)
- mid sm intestine connected to mini-stomach
- proximal sm intestine connected to mid sm int
- no IF produced
- pts need to receive IV B12
lipids in diet
- triacylglycerol
- phospholipids
- lycolipids
- sterols
- lipid-soluble vits : A, D, E, K
lipid digestion enzymes
-
cholesterol esterase aka nonspecific lipase
- digest CE → C
- can also digest diff lipids
-
lipases
- digest PL
-
pancreatic lipases
- digest TAGs
- need to be activated, bind with a colipase (bc you dont want them to be active without food and go and digest membrane PLs)
*short- and med-chain FAs that are generated are easily absorbed, long-chain FAs are more difficult
**we have some gastric lipases but they are v inefficient, so the int handles the vast majority of load
lipid dig/abs
- emulsification
- hydrolysis by gastric lipases
- more hydrolysis by pancreatic lipases
- emulsification/solubilization by bile salt micelles
- uptake of lipids
- resynth of lipids in ER (chylomicrons)
- exocytosis into lymph
emulsification overview
- stomach mixes and churns
-
duodenum is site of bile salt release
- CCK slows down gastric emptying, stimulates gallbladder contraction/bile release
- secretin stimulates release of bile and pancreatic bicarb
track: lipases from duodenum [action of panc lipases] into “circulation”
-
pancreatic lipase doesnt bind super-well to TAGs (has to compete with bile salts for purchase)
- colipase allows pancreatic lipase to bind even in presence of bile salts : can bind and digest TAG down to micelles
- micelles break up into constituents (incl FAs) as they get closer to the slightly acidic environment around the villi
- FAs can be absorbed through transporters
how does absorption actually happen?
- FFAs can diffuse
- everything else needs a transporter [2MG, lysoPL, chol]
-
once inside, lipids must be reassembled in the ER before exocytosed!!!
- packaged with betalipoproteins (which make them soluble) into lacteal lympatics
dig/abs of fat soluble vitamins
ADEK
- digestion: hydrolysis by pancreatic lipase releases vitamins
- absorption: dependent on absorption of dietary lipids
bile acid reabs
in distal ileum
- conjugated bile acids cotransported with Na
- unconjugated bile acids (more lipophilic) diffuse
from there, both get into enterohepatic circ and head back to liver
sites of absorption: fat and bile acid
- fat: passive reabs in prox sm intestine
-
bile acid: active reabs in distal ileum
- also some passive reabs in prox int, colon
effect of bile acid conc on lipid abs
if bile acid conc is above critical micelle concentration
- fat abs heavy in prox sm intestine
if bile acid conc is below critical micelle concentration
- fat abs light throughout sm intestine
causes of lipid malabs
- genetic
* CM metabolism defects - bile deficiency (block in release)
- pancreatic insufficiency (block in release of enzymes)
- other (secondary)
- tropical sprue
- Crohn’s disease/ulcerative colitis
- Zollinger Ellison - too much gastrin, too much acidity in stomach - gets into sm int, inactivates a lot of pancreatic enzymes!
- Celiac disease
**some of these knock out reabs SA
dig/abs of minerals
- digestion: release of protein-bound mineral
-
absorption: low efficiency! tightly controlled to prevent tox!
- other substances in lumen affect bioavailability
duodenal Fe abs
absorption (lumen into enterocyte)
- iron reductase takes Fe+3 and makes it Fe+2
- Fe+2 contransported with H via DCT1
- heme transported via heme transporter
- inside cell, heme oxidase breaks heme down into Fe+2
in epithelial cell, Fe+2 → Fe+3 via ferroxidase
-
storage pathway: Fe+3 stored in ferritin
- if unused, ferritin excreted when epithelial cells die/slough off
-
usage pathway: Fe+3 packaged with Fe binding protein
- move into blood via IREG1, binds with transferrin
Ca dig/abs
- Ca can move from lumen…
- into cell via transporters
- to plasma via paracellular transport
pathway for abs through cell
- low Ca triggers PTH release
- PTH circulates to kidney, activates catalyst for activation of vitamin D3/calcitriol
- activated calcitriol enhances transcription of Ca binding protein → aids in getting Ca over to basolateral Ca ATPase → pumping Ca out into plasma
GI tract receives/dumps in approx 9L of fluid daily, but only excretes 100mL in feces
intercellular aqueous channel = “shunt” pathway
- proximal to distal, the alimentary canal goes from leaky to tighter
ion transport throughout sm intestine
water will move with solute
duodenum
-
osmotically active particles: glucose, a.a.s
- lots of SGLT1 pulling in Na/glucose → water follows through aquaporins and paracellular jx
- what if there’s no food present?
- ions like Na can still pull water in
jejunum
- SGLT1 still in action
- Na/H exchanger working in conjunction with HCO3/Cl exchanger to move ions when there’s no food available
ileum
- tight jx are tighter (abs is more efficient)
- not much left to absorb, but still have electrolytes
- Na pulled in, water comes along
- when youre losing sodium: conservation!
- aldosterone secretion occurs, gets more Na back via enhanced colon EnAC transporters
in crypt cells
- driving force is CFTR secreting chloride
how does water get reabsorbed?
- aquaporins
- paracellular transport
water imbalance
diarrhea vs. steatorrhea
syndromes that enhance secretion
- mineral laxatives are osmotically active, draw out water - too much, can get diarrhea
- bile acids and lipids can irritate colon if theyre poorly reabsorbed so can cause increased secretion and diarrhea
- dumping syndrome : dumping too much chyme into sm intestine (more than can be digested) - too much solute pulls water out and causes diarrhea
