GIT Absorption

Question 1

What routes does the body use during absorption?

Answer 1

2 routes:

Transcellular path (through cells)

Paracellular path (between cells)

Question 2

What influences the paracellular pathway of absorption?

Answer 2

The ‘Tightness’ of tight junctions is influenced by Claudin proteins

Question 3

What does the tightness of TJ influence?

Answer 3

Determines whether/how much paracellular route is used

Colon has tight TJs, SI has ‘leaky’ tight junctions

Question 4

What is required for transcellular solute transport?

Answer 4

At least one solute has to be transported actively

Question 5

What influences the movement of solute paracellularly?

Answer 5

It is passive and inverse to resistance (dependent on the structure of tight junctions)

Question 6

What drives active transport in the gut?

Answer 6

Mostly the sodium potassium ATPase which sets up an electrochemical gradient. (Ensures sodium inside cells is extremely low and potassium relatively higher)

Question 7

How do carbohydrates get absorbed into the bloodstream?

Answer 7

Fructose passes through gut cell apical side via facilitated diffusion and then diffuses into blood stream via facilitated diffusion as well.

Glucose and galactose cross apical side via co-transport with Na+ (secondary active transport facilitated by Na+/K+-ATPase)

Question 8

How do proteins get absorbed into the bloodstream?

Answer 8

Amino acids are actively transported or secondary active transport via co-transport with Na+.

Dipeptides and tripeptides are co-transported with H+

The molecules that enter the cell from apical side can diffuse into the bloodstream on basolateral side.

Question 9

How do fats get absorbed into the bloodstream?

Answer 9

Short-chain fatty acids diffuse into cell from apical side then diffuse into blood stream on basolateral side.

Micelles break down into long-chain fatty acids and monoglycerides which then diffuse into the cell then form triglycerides which are packaged into lipoprotein complexes called chylomicrons in the cell which is released to lacteal of a villus

Question 10

What form must carbohydrates be in for absorption?

Answer 10

They need to be monosaccharides.

Question 11

How are starches broken down?

Answer 11

Alpha amylases to form 3 to 9 glucose polymers which are further broken down by maltase, lactase and sucrase

Question 12

Where does initial breakdown of starch occur?

Answer 12

In the mouth by ptyalin in saliva (20 - 40%)

Then it happens again by pancreatic amylase (50 - 80%)

Question 13

What enzyme breaks down maltose?

Answer 13

2 enzymes:

Maltase and alpha-dextrinase

Question 14

What enzymes break down lactose and sucrose?

Answer 14

Lactase and Sucrase

Question 15

How is fructose absorbed in the gut?

Answer 15

Facilitated diffusion in (across apical membrane via GLUT5) and then facilitated diffusion out (across basolateral membrane via GLUT2)

Question 16

How does glucose and galactose get absorbed in the gut?

Answer 16

SGLT1 (sodium/glucose cotransporter) using the Na+ gradient formed by Na+/K+ ATPase

Question 17

What is the maximum glucose absorption rate?

Answer 17

~120g/h

Question 18

What happens if sugar is not absorbed in large intestine?

Answer 18

Bacteria break it down resulting in diarrhoea + bloating and flatulence

Question 19

How are proteins digested into something that can be absorbed in the gut?

Answer 19

Digested in a stepwide fashion:

Proteases are secreted;

Somtach pepsins digest 10 - 15% of dietary protein

Pancreatic proteases (trypsin, chymotrypsin, carboxypolypeptidase, proelastase) convert 70% luminal protein to oligopeptides + 30% AA

Peptidases in enterocyte glycocalyx break down polypeptides into amino acids

Amino acids, dipeptides, and tripeptides can be absorbed as a result

Question 20

How is peptide/H+ co-transport facilitated?

Answer 20

+PepT1 co-transporter

Question 21

How is amino acid absorption facilitated?

Answer 21

Usually co-transported with Na+

Transporters are diverse due to differences between AA charges.

+PepT1 facilitates peptide/H+ co-transport

Question 22

How is basolateral absorption facilitated?

Answer 22

Basolateral transport occurs via amino acid specific transporters

Question 23

When is endoctosis used for absorption of proteins?

Answer 23

It is very rarely used but is seen in infant IgAs

Question 24

What happens to tripeptides after being co-transported with H+ by +PepT1?

Answer 24

They are digested within the cell prior to absorption.

Question 25

How are triglycerides broken down?

Answer 25

Lingual lipase kicks off the breakdown

Pancreatic lipase does most of the work because at this stage fats are emulsified and made more water soluble which means they can be accessed by pancreatic lipase.

The result is the fatty acids are cleaved off in most of the triglycerides with the exception of some that hold onto the middle fatty acid. This results in a mixture of FFA and monoglycerides.

Question 26

How is cholesteral broken down?

Answer 26

It is also de-esterified and broken down via cholesterol esterase

Question 27

How is fat absorbed?

Answer 27

Can diffuse through bilayer but this is very slow.. So there are transporters located an apical membrane (eg fatty acid translocase [FAT/CD36]

In the cell they are then packaged for transport by being added to lipoproteins called chylomicrons.

They are then exocytosed into lacteals (SI lymphatic vessels) then secreted into bloodstream via thoracic duct -> subclavian vein)

Digested fats are then distributed to the rest of the body and to the liver.

Question 28

How are lipids transported after absorption?

Answer 28

Small intestine packages fats into chylomicrons which are then broken down by lipoprotein lipase in cells such as adipose tissue and muscle into chylomicron remnants which are transported into the liver where fatty acids are stored, metabolised, and used.

Liver then packages CMRs into VLDLs which then get broken down or built up in cells of adipose tissue and muscles becoming IDL then LDL before returning to the liver.

Cholesterol is loaded into HDL in adipose tissue and other body cells and transported to the liver when full. HDL is released into the blood initially empty and accumulates cholesterol from everywhere before it goes to the liver.

Question 29

What enzyme allows transfer of lipids between HDL and LDL?

Answer 29

CETP

Question 30

How are water and electrolytes absorbed?

Answer 30

Water: Mostly in small intestines via osmotic gradient

Electrolytes/minerals: Active or passive and used to set up the osmotic gradient required to move water across membranes.

Question 31

How is water balance maintained in the body?

Answer 31

2000 mls of water ingested daily

Endogenous secretions amount to 7000mls daily

8800mls are reabsorbed (5500 in jejunum, 2000 in ileum, and 1300 in colon)

200ml are lost in stool

Question 32

How is Na+ absorbed?

Answer 32

Na+/K+ ATPase driving transport of other stuff in the intestine.

In the colon there is a Na+ channel which allows for absorption of Na+ from apical membrane which is followed by more Na+/K+ ATPase action

Question 33

How is chloride used by the body?

Answer 33

It follows sodium and is absorbed mainly via passive diffusion (transcellular AND paracellular) as well as Na+/H+ and Cl-/HCO3 exchange

Question 34

What is Cl- secreted for?

Answer 34

It allows a change in viscosity of the mucous lining digestive tract.

Question 35

Which channel is mutated in cystic fibrosis?

Answer 35

CFTR

Question 36

How is Cl- regulated?

Answer 36

via cell volume (turgor of the cell) or signalling

Question 37

How is K+ absorbed into the blood?

Answer 37

Na+/K+ ATPase makes transcellular absorption very energy costly due to the concentration gradient. So absorption is done via paracellular diffusion (90%)

in colon there is active K+-H+ exchange for fine tuning purposes.

Question 38

How is K+ secreted?

Answer 38

Concentration gradient created by Na+/K+ ATPase allows easy diffusion of potassium via pores in apical membrane.

Question 39

What factors affect mineral absorption?

Answer 39

Must first be digested and soluble.

Bioavailability which is affected by:

pH

Redox state of metal (Fe3+ is highly insoluble)

Dietary complexes which enhance solubility (ascorbate for example uses this)

Dietary complexes which diminish absorption (eg carbonate in water makes calcium unabsorbable)

Question 40

How is magnesium absorbed?

Answer 40

Mg2+ is pumped out of the cell on basolateral membrane using ATP

Mg2+ diffuses into the cell via TRPM6 membrane protein channel which uses the magnesium ion gradient drag.

Some magnesium can’t enter the cell when bound to phytate, fiber, and fatty acids.

Question 41

How is calcium absorbed?

Answer 41

Same as magnesium except there are 2 pumps for calcium on basal membrane (PMCA1b Calcium ATPase and a Na+/Ca2+ ATPase antiporter)

In the blood half of the calcium is bound to albumin and in enterocytes calcium is bound to calbindin.

On apical side the TRPV6 (which is regulated by vitD) allows influx of calcium into the cell where it immediately binds to calbindin.

Some calcium is absorbed via paracellular path (this process is slow and not very effective)

Question 42

What are the forms of dietary iron?

Answer 42

2 forms:

Haem iron: Iron in meat-blood or muscle, bound to haem and this is more readily absorbed than non-haem iron

Non-haem iron: Iron in vegetables which is either ferrous (Fe2+) or Ferric (Fe3+) and is absorbed in duodenum before neutralization.

Only about 10% of ingested iron is absorbed.

Question 43

How is iron absorbed?

Answer 43

Haem iron is absorbed via HT protein and non-haem iron by DMT1.

Free Fe2+ iron is produced from both transported iron.

Ferroportin channel is present on basal membrane which allows iron to diffuse into the blood.

Rest of the iron that isn’t needed yet is complexed with ferritin and stored. Then the cell dies and then it is shed into GI tract before it is excreted in faeces.

In the blood Fe2+ is converted into Fe3+ and that binds to Fe3+-TF which is then used to transport.

Fe3+ is converted to Fe2+ via reductase

Question 44

How is ferroportin channel closed?

Answer 44

Via a protein called hepsedin produced by the liver.

Question 45

How are vitamins A, D, E, and K absorbed?

Answer 45

ADEK are absorbed exactly the same way as fats

Question 46

How are water-soluble vitamins absorbed?

Answer 46

All have their own specific channels.

Question 47

How is folate absorbed?

Answer 47

In nature has lots of glutamate residues. These are all removed except for 1 via a membrane protein on enterocytes called folate conjugase (this is rate limiting).

Then folate with 1 glutamate can enter the cell and is antiported with OH-.

Dihydrofolate reductase reduces folate and adds 5 methyl groups to it.

The resultant methyl-tetrahydrofolate is transported across the basal membrane which is a bioactive molecule.

Question 48

How is vitamin B12 absorbed?

Answer 48

Cobalamin (B12) is released from dietary protein due to acid pH and pepsin release.

Gastric glands release haptocorrin and gastric parietal cells release intrinsic factor but only haptocorrin can bind to cobalamin at this stage.

Haptocorrin is released after pancreas breaks down the protein with its proteolytic enzymes.

CBL binds to Intrinsic Factor which then gets endocytosed after IF binds to a receptor on enterocyte apical side.

CBL is then released from vesicle and binds to transcobalamin II which is then released into the bloodstream.

Transcobalamin II receptor is present at target locations.