Digestion and Absorption

Question 1

Remember that the stem cells of the GI tract are located in the intestinal crypts and they migrate up the villi to differentiate into enterocytes, goblet cells, or endocrine cells. Also cells can migrate down the villi to differentiate into pana cells, defense cells

Remember that cells in the crypts are mostly secretory and the cells in the villus are more absorptive

Question 2

T or F. There is a very high proliferation rate in the intestine

Answer 2

T. Very 3-5 days all cells will replace themselves as a protective mechanism against damage/mutation

Question 3

Trypsin breaks carboxyl terminal bonds of basic peptides like arginine and lysine

chymotrypsin breaks N-terminus bonds of aromatic AA bonds (elastase is similar but broader)

Question 4

Note that there are two main categories/locations of digestion in the Gi tract, lumenal digestion which is mediated by secreted enzymes mainly from the pancreas, and membrane-digestion which is mainly mediated by brush-border dissaccharidases such as maltase, sucrase, lactase, etc.

Question 5

What are the main layers/barriers that a molecule must pass to be absorbed from the GI tract?

Answer 5

1. The undisturbed mucosal layer
2. The glycocalyx layer
3. The epithelium, cytoplasm, and then basolateral membrane

Question 6

What are the main mechanisms of GI absorption?

Answer 6

1) Pinocytosis- simple invagination of the epithelium of the villi (very little). Note that proteins mostly arent absorbed by the small intestine, but those that are, are mediated by pinocytosis
2) Passive diffusion via paracellular (leakly in small intestine) routes for only some molecules (semi-permeable)
3) Facilitated diffusion
4) Active transport (Na, sugars, AAs)

Question 7

How does the GI respond to starvation or resection?

Answer 7

During starvation the villi shorten and some digestive enzymes do not proliferate, but during resection you will initially see undernutrition but the remaining tissue will expand and adapt

Malnutrition doesnt really occur until 70% of the small intestine is removed/damaged

Question 8

Digestion of carbs

Answer 8

Luminal digestion of carbs is mediated by salivary a-amylase in the mouth (break a1,4-glycosidic bonds to form maltose, maltotriose, and limit dextrin) and pancreatic a-amylase in the small intestine

Membrane digestion is mediated by glucoamylase, sucrase, isomaltase, lactase, and trehalase

Note that the body has a very high carb digestive capacity so that pretty much everything we eat is digested

Question 9

Question 10

What are the main products of GI digestion to be absorbed?

Answer 10

glucose

galactose, fructose

Question 11

The vast majority of glucose absorption is aerobic and via active transport

Question 12

How is glucose absorbed from the GI lumen?

Answer 12

1) SGLT 1, which is a Na/Glucose co-transporter that depends on a gradient of sodium which is maintained by active sodium transporters on the BL membrane
2) GLUT 2-BL (glucose, galactose, and fructose) and 5-apical (glucose and fructose). These are Na independent (more facilitated than active)

These have a VERY high absorptive capacity (and is not very regulated- dont overdo it)

Question 13

Answer 13

Sucrase-Isomaltase normally presents in children because they only express lactase in early childhood and then switch primarily to sucrase-isomaltase expression and this can occur when the timing messes up

A: Normal

B: Absence of SGLT2

C: Overall impaired absorption

Question 14

How much protein are adults exposed to on a normal day?

Answer 14

About 100g dietary and another 40g from secretions, cellular degeneration, etc. Note that all of this is acted upon by proteases in the GI lumen

Question 15

How is trypsinogen secreted from the pancreas activated?

Answer 15

Once it reaches the duodenum, enterokinase from duodenal cells cleaves a 6 AA residue from the C-terminal end to produce active trypsin. Trypsin then activates the other pancreatic enzymes, as well as more trypsin

Question 16

What predominantly causes acute pancreatitis? Chronic?

Answer 16

Acute: Biliary obstruction and alcohol

Chronic: alcohol

Question 17

What is the mechanism of pancreatitis?

Answer 17

there is premature activation of trypsin in the pancreas caused by interaction of trypsinogen with pancreatic lysosomes (which contain enterokinase) or genetically due to a R117H mutation (prevents inactivation/stabilizes) that causes pancreatic destruction

Question 18

There are many types of free AA transporters including Na dependent transporters, PAF proteins (driven by NHE) and facilitated diffusion as well, specific for basic, acidic, neutral AAs

Large peptides are broken down further by brush border peptidases

Answer 18

Note that the absorptive capacity of di- and tripeptides is greater than that of free AAs suggesting seperate carrier systems for them, predominantly in the proximal intestine (whereas free AA transporters are more clustered in the distal small intestine). These are coupled to NHE

Question 19

Question 20

Note that if you present arginine as a dipeptide it will be absorbed better b/c its absorbed using a different transporter

Question 21

How is fat absorbed?

Answer 21

This requires the presence of bile and lipases and emulsification (breaking down for action with lipases). Lipases include gastric lipase (breaks down the fatty acid/glycerol bond at position 3) producing diglycerides

Monoglycerides and free fatty acids can be absorbed

Question 22

What are the products of lipids being hydrolyzed by lipases?

Answer 22

cholesterol

fatty acid

monoglycerides

Question 23

What happens to the monoglycerides, fatty acids, and cholesterol?

Answer 23

They form mixed micellese are diffuse across the lumenal membrane via passive diffusion (may be facilitated), but the entire micelles are not absorbed all together so the carriers may be different

Once in the cytosol, these particles are insoluble again and are transported by binding to fatty acid binding proteins to the smooth ER where the triglycerides are re-synthesized using acyl CoA and ATP and then packaged into chylomicrons

Question 24

How are chylomicrons produced in the small intestine?

Answer 24

They are composed of mostly TAGs and they are formed via 2 parts:

1) Formation of a particle 1 (Apo-B + core lipid) formed in the RER
2) Particle 2 is formed in the SER
3) These particles combine to form a pre-chylomicron

The pre-chylomicron that budds of the ER using a PCTV and acquires a Apo-A1 in the golgi, and then is exocytosed into lymph (not blood like carbs and proteins)

Question 25

What are some conditions that lead to steatorrhea?

Answer 25

1. Rapid gastric emptying
2. Defect in pancreatic enzyme secretions
3. Interrupted enteroheaptic circulation (bile is needed to solublize lipids for absorption!!)
4. Qualitative deficit of bile acids
5. Inadequate chylomicron formation or Defect in lymph transport of chylomicrons (both lead to backflux)

Question 26

Why would rapid gastric emptying lead to steatorrhea?

Answer 26

Pumping that much acid into the duodenum can overcome the neutralzation by HCO3- and pancreatic enzymes cannot be activated in too low of pH

Question 27

How are most fat and soluble vitamins absorbed?

Answer 27

passively, with fat soluble vitamins such as A,D,E, and K forming bile salt mixed micelles for absorption

Question 28

Which vitamins require Na-dependent active transport for GI absorption?

Answer 28

Thiamine B1), Vit C, folate (Duo and upper jej), B12 (ileum)

Question 29

How is riboflavin (B2) absorbed?

Answer 29

facilitated diffusion

Question 30

Question 31

How is calcium absorbed from the GI?

Answer 31

via channels like TRPV, voltage gated, and then calcium binds to CaBP (calbindin) for transport across the cell to the BL membrane where it is absorbed via CaATPase (active)

NOTE: VitD (via PTH) upregulates transcription of CaBP

Question 32

How is iron absorbed form the GI?

Answer 32

In the villi region there is a transporter called DMT1 for Fe2+ (Fe3+-ferric cannot be absorbed- Fe3+ can be converted to Fe2+ via DCYTB) that absorbs iron. Iron is then bound to transferrin and either stored as ferritin or transported into blood via ferroprotein-1 (FPN1)

Also in the crypt region of the GI, there is a Fe-transferrin apical receptor for internalization (the receptor recycles)

Question 33

Almost all fluid is reabsorbed!! Dont want to be shitting everywhere

Question 34

Note that there are two main paracellular pathways- leaky and pore pathways. The pore pathway is mediated by Claudins, like claudin 2 in the duodenum and proximal jejunem which allows passage of Na+ and K+ (cations). So most Na and K is absorbed in the proximal intestine where the Cldn 2 molecules are, mainly driven by hydrostatic and osmotic gradients from food/drink

Question 35

Na can also be absorbed transcellularly from the apical membrane driven by a BL Na/KATPase and via co-transporters (e.g. Na/Cl and Na/glucose), as well as NHEs (D)

A, B, and D are mostly found in the proximal intestine and C is found mostly in the distal

Question 36

This occurs predominantly in the very distal ileum and colon (this is why the GI tract becomes more alkaline as it approaches the colon)

Note that distally induced diarrhea would lead to metabolic acidosis unlike vomiting

Question 37

In the colon K+ is actually secreted. So K+ will also be lost in diarrhea

Question 38

Water is absorbed primarily via an osmtoic gradient as Na and K are absorbed. Note that the GI lumen is almost iso-osmolar to the blood in the duodenum and becomes hypo-osmolar in the distal GI due to the efficiency of Na and K absorption in the proximal GI

Diffusion of water, Na, or K does not occur in the colon

Question 39

T or F. In the small intestine, the net effect of the absorption AND secretion of electrolytes like Na and K is absorption

Answer 39

T. Although both occur

Question 40

Secretion of electrolytes in the small intestine

A: VIP, Secretin, prostaglandins- all icnrease secretion of Cl-

Question 41

Question 42

___% of pancreatic lipase has to be dysfunctional/absent to cause steaorrhea

Answer 42

80%. This is a trend with the GI in that it typically takes a large decrease/increase/dysfunction of something to change the status-quo of absorption/digestion/secretion/etc.

Question 43

Question 44

Insulin (like leptin from adipocytes) reduces food intake by acting directly at the hypothalamus!

Question 45

How does insulin affect appetite and metabolism?

Answer 45

It acts on the hypothalamus to decrease appetite and increase metabolism

Question 46

How does leptin affect appetite and metabolism?

Answer 46

it acts on the hypothalamus to downregulate NPY, AgRP and upregulate POMC to promote decreased appetitie and increased metabolism

Question 47

How does CCK affect appetite and metabolism?

Answer 47

It is released from I cells of the duodenum to act on vagal affarents to the brain to decrease appetite and decrease gastric emptying (increases satiety)

Question 48

How does PYY affect appetite and metabolism?

Answer 48

It is secreted by L cells of the ileum and colon and acts on the hypothalamus to downregulate NPY and AgRP and upregulate POMC to promote decreased appetite and increase gastric emptying

Question 49

How does ghrelin affect appetite and metabolism?

Answer 49

it is released from endocrine cells of the oxyntic gland area of the stomach and acts on the hypothalamus to upregulate the NPY and AgRP neurons to promote increased appetite and decreased gastric emptying (the exact opposite of PYY)