Gastro - Ions Flashcards

1
Q

What is diffusion, what decides its rate and why do mammals evolve circulatory systems?

A

In general, diffusion is the process whereby atoms and molecules intermingle because of their random thermal motion. Diffusion occurs rapidly over microscopic distances, but slowly over macroscopic distances. Multicellular organisms, such as humans, evolve circulatory systems to bring individual cells within the diffusion range.

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2
Q

What does the cell membrane act as? which types of molecules are easily diffused?

A

The cell membrane acts as a diffusion barrier, enabling cells to maintain cytoplasmic concentration of substances different from their extracellular concentrations. Lipid soluble molecules can cross more easily than water soluble molecules.

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3
Q

Define osmosis

A

The definition of osmosis is the diffusion of water from a hypotonic to a hypertonic medium

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4
Q

how can molecules cross the epithelium to enter the bloodstream?

A

In general, molecules can cross either from the paracellular transport through tight junctions and lateral intercellular spaces, or via transcellular transport through the epithelial cells In general concepts, the solutes can cross the cell membrane by simple diffusion, facilitated transport or active transport. And it can be transported either via channel proteins or carrier proteins.

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5
Q

Differences between channel and carrier proteins

A

Channel proteins form aqueous pores allowing specific solutes to pass across the membrane, whereas carrier proteins bind to the solute and undergo a conformational change to transport the solute across the membrane. In general, channel proteins allow much faster transport and then carrier proteins. A carrier protein has a solute binding site which then transforms in shape and allows it to open up and go across the lipid bilayer, whereas a channel protein opens up to a specific solute and allows it to go across a gradient.

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6
Q

Uniport vs couples transport

A

you could either have an uniport carrier transport or coupled transport in which another ion is co-transported with the solute. In uniport it only involves one solute across the membrane, whereas in coupled transport it involves another ion. And that could be either a symport in which both the ion and the coupled ion go in the same direction, or antiport in which the ion and the coupled ion go in an opposite direction across the membrane.

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7
Q

Types of AT

A

Active transport requires energy. It can be either primary active transport, which is linked directly to cellular metabolism and uses ATP. Or secondary active transport, which derives the energy from the concentration gradient of another substance that is actively transported.

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8
Q

Examples of 2AT, FT

A

Examples of secondary active transporters include SGLT-1, bicarbonate and chloride counter transport, and sodium and hydrogen counter transport involved in pancreatic bicarbonate secretion. And examples of facilitated transport includes GLUT-5 and GLUT-2 in small bowel absorption of monosaccharides

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9
Q

Absorption of carbohydrates involved which carrier proteins

A

The absorption of carbohydrates involving glucose and galactose is secondary active transport done by a carrier protein SGLT-1 on the apical membrane. This protein can transport glucose uphill against its concentration gradient, so it’s effective when glucose levels in the lumen are below those in the enterocyte, for example. Fructose, or the absorption of fructose, is by facilitated diffusion, and this is via the GLUT- 5 on the apical membrane This is effective at relatively low concentrations of fructose in the lumen as tissue and plasma levels are generally low.

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10
Q

How is the exit of glucose facilitated at the BLM

A

Then at the basolateral area, the exit of glucose is by facilitated diffusion using GLUT- 2 which is a high capacity, low affinity facilitative transporter, and glucose between plasma and tissue
enterocytes are generally equilibrated that way.

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11
Q

How is water absorbed in the GI tract?

A

Ninety nine percent of water that is presented to the GI tract is absorbed. The absorption of water is powered by the absorption of ions. The greatest amount of water is absorbed in the small intestine, especially in the jejunum, which contains a large volume of microvilli.
Many ions are slowly absorbed by passive diffusion in this process.

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12
Q

How much water is absorbed? `How is this possible when only a little is ingested?

A

In general, there is approximately 8 litres of water a day absorbed in the small bowel and approximately 1 . 4 litres of water a day is absorbed in the large bowel. we probably have a maximum of two litres ingested a day, but we produce about a litre of saliva a day, in addition to two litres of gastric secretions. And to add to that, we have bile secretion, pancreatic secretions and intestinal secretions, which contributes to a large volume of water in our intestines.
This in turn, is then absorbed in the small bowel, as we said, in about 8 litres, and the colon absorbs the rest of the water we have.

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13
Q

How is water absorbed? How is sodium absorbed?

A

The absorption of water is through a standing gradient osmosis, which is driven by sodium. Transport of sodium from lumen into the enterocytes is usually complex and varies between species, and it varies also along the line of the small bowel. It involves counter-transport in exchange for hydrogen in the proximal bowel,
co-transport with amino acids and monosaccharides in the jejunum, co-transport with chloride in the ileum,

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14
Q

How is chloride co transpoted? How is potassium diffused?

A

Chloride is co-transported with sodium and is exchanged with bicarbonate in the colon into enterocytes. Both of these happen as a secondary active transport. Potassium diffuses in via paracellular pathways in the small intestine, and leaks out between cells in colon, which is a passive transport process.

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15
Q

what happens to this intracellular sodium?

A

The active transport of sodium into the lateral intracellular spaces by sodium, potassium ATPase transport in the lateral plasma membrane Chloride and bicarbonate is transported then into the intercellular spaces due to the electrical potential created by the sodium transport.

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16
Q

What does the high conc of ions cause? Where is this?

A

The high concentration of ions in the intercellular space causes fluid there to be hypertonic because it’s concentrated with these ions. And therefore osmotic flow of water from the gut lumen via adjacent cells and the tight junction’s into these interstellar spaces. So water then distends the intercellular channels, and in turn causes increased hydrostatic pressure. And this then results in the ions and water moving across the basement membrane of the epithelium, and then are carried away by the capillaries.

17
Q

What can calcium do in the small bowel?

A

as we present calcium to the lumen of our small bowel, it can diffuse across either in the paracellular channels, or via the cells itself. Once across here, via the IMcal channels, it binds to calbindin and therefore that prevents the presence of high concentration of calcium within the cell.

18
Q

Where does calcium bind?

A

It binds to calbindin, and then it gets presented to either a channel to immediately take it across the basement membrane or it gets exchanged for sodium So there’s two ways of crossing the calbindin and the calcium across the basolateral membrane.

19
Q

what are the implications for transport of calcium into the cell from the lumen?

A

Calcium acts as an intercellular signalling molecule, and we need to transport calcium while maintaining a low intracellular concentration and that’s why calbindin is important. it binds to calbindin in the cytosol and preventing its action as an intracellular signal. Calcium is then pumped across the basolateral membrane by plasma membrane calcium ATPase, or PMCA, against a concentration gradient. And this membrane, or this process, has a high affinity for calcium, but it has a low capacity. So it can attract calcium quite a lot, but it has very little capacity for it. This process maintains the very low concentration of calcium normally observed within a cell.

20
Q

What does a sodium exchanger in a calcium context?

A

calcium can be pumped across to the basolateral membrane by the sodium calcium exchanger against the concentration gradient. This one has a low affinity for calcium, but a high capacity. So we can exchange a lot of calcium, but it has a low attraction to it requiring a larger concentration of calcium to be effective

21
Q

what are the actions of vitamin D on calcium?

A

Vitamin D is essential for normal calcium absorption, it enhances the transport of calcium through the cytosol, it increases the levels of calbindin and it also increases the rate of extrusion across the basolateral membrane by increasing the level of calcium ATPase in the membrane itself.

22
Q

What types of iron can we ingest? What are their fates?

A

when we ingest iron in food, it can be either heme iron or non-heme iron. Heme iron is absorbed directly through a transporter and then goes into the intracellular area. Whereas the non-heme iron is presented to us as ferrous form of iron. And this ferrous form is not absorbable readily. So we need to change that into a ferric form, which is usually done by the duodenal Cytochrome B agents. This in turn, when it is in the ferric form, the iron is then absorbed via this channel into the intracellular area.

23
Q

What can iron now do in the intracellular area?

A

Once we have iron in the intracellular area, it can be either stored as ferritin or it can be absorbed across the basolateral membrane via the Ferroportin channel into the other side. the ferric form needs to be then changed again into the ferrous form so it can be transported in the blood system or in the capillaries, this is usually done via transferrin, so ferrous attaches to transferrin and then transferrin is taken across the capillaries either to the bone marrow or deposited in the liver

24
Q

What control iron absorption?

A

In the liver, once we have enough iron absorbed, the liver produces hepcidin which then controls Ferroportin, and it reduces the production of Ferroportin. So that the negative pathway of how we stop excessive iron absorption.

25
Q

What are the implications for iron absorption?

A

adults ingest 20approximately milligrams of iron per day, but only absorb about 1.5 milligrams per day. So iron is present, in diet, either as inorganic iron or as part of heme iron.

26
Q

Why is vitamin C important?

A

Vitamin C is important, and this reduces the ferric to ferrous iron.

27
Q

A note on heam iron

A

A note on heme iron, is usually a smaller part of the diet, but they are more readily absorbed There is evidence that the absorption of heme iron is directly done by a heme carrier protein, HCP- , and via receptor-mediated endocytosis, whereas ferrous is liberated by Heme oxygenase.

28
Q

What are vitamins?

A

Vitamins in general are organic compounds that cannot be manufactured by the body, but vital for metabolism.

29
Q

Where is vitamin b12 stored? What does a lack result in ?

A

vitamin B12 , the liver contains a large store of this, up to 5 milligrams. Impaired absorption of vitamin B12 retards the maturation of red blood cells. And this is usually seen in pernicious anaemia, in patients who have low vitamin B12 . Most vitamin B12 is usually presented to ua in food, is usually bound to proteins

30
Q

What happens upon ingesting b12?

A

But if you think of dietary vitamin b12 , it’s usually attached to a protein. And when this compound reaches the stomach, it gets separated because the protein gets destroyed by the acid. The vitamin B12 then attaches to haptocorrin, which is produced in our saliva. And that is important because this compound of haptocorrin and B12 , prevents the destruction of vitamin B12 by acid in our stomach. So it allows it to go across the duodenum, and once it crosses the duodenum the haptocorrin is digested and then we
have B12 freely in our jejunum and ileum.

31
Q

What does b12 do once free in small bowel?

A

Once it’s free in our small bowel, the vitamin B12 , then attaches itself to intrinsic factors. Intrinsic factors are produced from our parietal cells in the stomach, actually And they meet in the small bowel and they attach to each other. This compound is then absorbed in the ileum. And then crosses across into the capillaries, and then in the capillaries the vitamin B12 attaches itself to transcobalamin, which is usually produced in the ileum. And then this compound is then readily presented to the liver where it gets stored.

32
Q

how is the denaturation of B12 in the stomach avoided?

A

It basically attaches itself to haptocorrin, which is released in saliva and also from the parietal cells of the stomach. These R proteins, or haptocorrin, attaches to the B12 , but then gets digested in the duodenum before it releases the B12 into the small bowel

33
Q

overview of b12 absorption

A

So this compound, vitamin B12 attached to intrinsic factor is the only way that we can absorb vitamin B12 . This complex binds to cuubulin receptor and it’s taken up in the distal ileum. Once in the cell, this complex of vitamin B12 and intrinsic factor is broken, possibly in the mitochondria. It then crosses the cell, and attaches to transcobalamin, and then travels to the liver bound to transcobalamin.