Digestion and Absorption - Jacinto 2/25/16

Question 1

overview of digestion and absorption in intestine

Answer 1

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

Question 2

surface area amplification

Answer 2

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

Question 3

intestinal villi structure

Answer 3

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

Question 4

transport of nutrients across enterocyte

types of transporters

Answer 4

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

Question 5

carbs in the diet

Answer 5

• plant starch: amylopectin, amylose
• dietary fiber: cellulose
• animal starch: glycogen
• disaccharides: sucrose, lactose
• monosaccharides: glucose, fructose

Question 6

carb breakdown: amylases

Answer 6

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

Question 7

carb breakdown

luminal vs membrane digestion

Answer 7

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

Question 8

abs of dietary carbs

Answer 8

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

Question 9

carb maldigestion

[lactose intolerance]

Answer 9

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

Question 10

bacterial fermentation in lactose intolerance

why is it a good thing?

Answer 10

bacterial fermentation of lactose that makes it to the colon produces H2 gas as well as short chain FAs

1. salvages calories from lactose that cant otherwise be gotten
2. reduces water loss in feces
3. combats int inflammation: FAs can support regulatory T cells in gut immune system

Question 11

carb dig/abs abnormalities

Answer 11

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

Question 12

proteins in diet

Answer 12

• animals and plant sources
• endogenous proteins: recycling of proteins from digestive enzymes, dead epithelial cells

Question 13

digestion of proteins

Answer 13

• 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

Question 14

protein digestion

luminal vs membrane digestion

Answer 14

luminal digestion

• pepsin, pancreatic proteases

membrane digestion

• peptidases in brush border to break down large peptides
• carrier proteins that can move di/tripeptides in

Question 15

enzymes involved in protein digestion

Answer 15

• 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]

Question 16

di- and tripeptides

Answer 16

once in cells, di- and tripeptides are further digested by cytoplasmic peptidases → a.a.s, which move into bloodstream

Question 17

protein absorption

Answer 17

1. passive transport
2. [majority] Na-a.a. cotransport
   * NHE can drive absorption by setting up gradient

absorption is efficient, but not as efficient as carbs

Question 18

protein dig/abs abnormalities

Answer 18

1. 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

2. pancreatic insufficiency
3. other

• decreased surface area
• surgery
• parasitic infection

Question 19

nucleoprotein dig/abs

Answer 19

digestion

• pancreatic DNase, RNase
• polynt hydrolysis via brush border phosphodiesterases and nucleotidases

absorption

• nucleoside transporters
• uric acid excreted in urine
• sugar reabsorbed into circ

Question 20

dig/abs of vitamins

Answer 20

• 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

Question 21

absorption of B12/cobalamin

Answer 21

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

Question 22

ways B12 abs could be compromised

Answer 22

• lose ileum
• not secreting IF
• defects in R protein [if you cant get your pancreatic enzymes to get R protein off]

Question 23

Roux en Y surgery

Answer 23

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

Question 24

lipids in diet

Answer 24

• triacylglycerol
• phospholipids
• lycolipids
• sterols
• lipid-soluble vits : A, D, E, K

Question 25

lipid digestion enzymes

Answer 25

* **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

Question 26

lipid dig/abs

Answer 26

* 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

Question 27

emulsification overview

Answer 27

* _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

Question 28

track: lipases from duodenum [action of panc lipases] into "circulation"

Answer 28

* **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

Question 29

dig/abs of fat soluble vitamins

Answer 29

ADEK * _digestion_: hydrolysis by **pancreatic lipase** releases vitamins * _absorption_: dependent on absorption of dietary lipids

Question 30

bile acid reabs

Answer 30

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

Question 31

sites of absorption: fat and bile acid

Answer 31

* **fat:** passive reabs in prox sm intestine * **bile acid:** active reabs in distal ileum * also some passive reabs in prox int, colon

Question 32

effect of bile acid conc on lipid abs

Answer 32

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

Question 33

causes of lipid malabs

Answer 33

1. genetic * CM metabolism defects 2. bile deficiency (block in release) 3. pancreatic insufficiency (block in release of enzymes) 4. 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

Question 34

dig/abs of minerals

Answer 34

* **digestion:** release of protein-bound mineral * **absorption:** low efficiency! tightly controlled to prevent tox! * other substances in lumen affect bioavailability

Question 35

duodenal Fe abs

Answer 35

_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**

Question 36

Ca dig/abs

Answer 36

* 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

Question 37

GI tract receives/dumps in approx 9L of fluid daily, but only excretes 100mL in feces

Answer 37

intercellular aqueous channel = "shunt" pathway * proximal to distal, the alimentary canal goes from leaky to tighter

Question 38

ion transport throughout sm intestine

Answer 38

**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

Question 39

water imbalance diarrhea vs. steatorrhea

Answer 39

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