Onwards Flashcards

1
Q

Where does final digestion take place? What are some characteristics of this place?

A

Takes place on the lumenal surface of the cells lining the gut - they are called enterocytes and have a large SA due to infoldings, which make villi and microvilli.
These infoldings are the brush border.

Absorption and hydrolysis of di- and tripeptides take place here as well

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2
Q

What are digestive enzymes secreted as?

A

Proenzymes

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3
Q

What regulates secretion?

A

Secretagogues

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4
Q

How does food move through the digestive tract?

A

Food moves through the digestive tract by wavelike muscle contractions.

In the GI tract, smooth muscle contracts in sequence to produce a peristaltic wave, which propels chewed material along.

Peristalsis comprises relaxation of circular smooth muscles; their contraction behind the food is to stop it moving backward; then longitudinal contraction to push it forward.

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5
Q

How does food get to the stomach and what are the characteristics of this?

A

Food passes through the Oesophagus, between the mouth and the stomach. This is what connect the mouth to the stomach.

It is lined with flattened (squamous) epithelial cells which do not have mechanisms to digest or absorb nutrients.

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6
Q

What is Mucosa? And what is the advantage of it?

A

Mucosa (mucous membrane) means the moist surface of any hollow organ, that communicates with the outside world. Secrets mucus, to acts as a barrier to pathogens and prevent tissues becoming dehydrated.

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7
Q

What is Lamina Propria?

A

It is the connective tissue layer of a mucous membrane; along with epithelial cells, it forms the mucous membrane.

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8
Q

Explain how complex carbohydrates and proteins are digested?

A

The first job in the digestion of these, is to first chop them up from their long chains, into smaller chains, then into the individual component parts.

A lot of this digestion is carried by pancreatic enzymes, which delivers amino acids and di- and tripeptides.

These are then actively transported across the luminal surface of the epithelial cell – the enterocytes that line the GI tract.

These are then able to passively diffuse into the blood.

The blood eventually drains into the hepatic portal vein. This vein goes straight from the GI tract into the liver.

So the liver has high concentrations of these nutrients.

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9
Q

Which organ is best to deal with monosaccharides and amino acids?

A

The liver

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10
Q

Is fat water soluble?

A

No!

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11
Q

What is the function of bile salts?

A

Helps to emulsify the fats.

Helps to form micelles of fatty acids; which brings the fatty acids into close contact to the brush border.
The fatty acids are then transported into the epithelial cells.

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12
Q

Explain how Bile Fats work?

A

One end of the bile salt is hydrophobic – likes the fat environment, and one end is hydrophilic – likes the aqueous environment.

So you form these droplets which are fairly stable.

This then forms an emulsion, which has a large surface area.

The lipase enzymes start cutting off the fatty acids from the glycerol background.

This delivers a mixture of free fatty acids and monoglycerides (one fatty acid attached to a glycerol).

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13
Q

What happens to the free fatty acids and monoglyceride after being cut by lipase enzymes?

A

The free fatty acids and monoglycerides are re-constituted to make triglyceride (glycerol backbone with three fatty acids).

These are then further packed into chylomicrons.

The Chylomicrons are then secreted into secreted vesicles.

Then into the lacteal.

This bypasses the liver and delivers chylomicrons into the general circulation. So that these triglycerides can be delivered into the adipose cells for storage.

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14
Q

Are lipids water soluble?

A

No!

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15
Q

How are lipids transported?

A

Because they are not water soluble, they cannot be transported as they are, in plasma.

Instead, the enterocytes package them into lipoprotein particles called chylomicrons. These are then transported away from the GI tract in lymph vessels (the lacteal system) to avoid first-pass exposure to the liver.

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16
Q

What proteins are in the salivary glands?

What do these proteins do?

A

Amylase and Lysozyme

Amylase breaks down starch and Lysozyme breaks down proteins.

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17
Q

What proteins are in the stomach?

What do these proteins do?

A

Pepsin A and Gastric lipase

Pepsin A is a protease that breaks down proteins and amino acids.

Gastric lipase digest fats

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18
Q

What proteins are in the pancreas?

What do these proteins do?

A

Trypsin, Chymotrypsin, Elastase - these are all protease enzymes

Carboxypeptidase A and B – chop smaller protein chains

Pancreatic lipase – digest fats and glycerides into their free-fatty acids

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19
Q

Which enzymes are on the lumenal of the small intestine Epitheilial cells?

A

Di- and oligosaccharides, aminopeptidase, dipeptidases etc.

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20
Q

Which transport is in the lumenal of the small intestine Epitheilial cells?

A

Na+ - monosaccharide co-transport (SGLUT-1)

It is an active transport that drives sodium uptake.

As well as facilitated fructose transport (GLUT-5) etc.

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21
Q

Which enzymes and transport systems are present in the contra lumenal?

A

Na+/K+ ATPase and Adenylate cyclase

Facilitated monosaccharide transport (GLUT-2)

Facilitated neural amino acid transport

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22
Q

Why are transport systems used by enterocyte cells (cells that line the GI tract)?

A

To ensure that even low concentrations of nutrients are removed from the lumen of the gut.

This leads to high intracellular nutrient concentrations, allowing passive transport from the cells to the blood.

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23
Q

What is known as the engine of active transport across the endothelial?

What is it responsible for?

A

Na+ / K+ ATPase - a primary active transport system.

Responsible for keeping the potassium ion; NOT ATPase.

24
Q

Explain how Na+ / K+ ATPase works?

A

It uses ATP to drive the transport of sodium up its concentration gradient out of the cell, whilst allowing potassium to come in; tis generates a membrane potential.

25
Q

What is a primary active transport system?

A

A system that directly uses chemical energy to transport all species of solutes across a membrane against their concentration gradient.

26
Q

What is the concentration of sodium in the lumen and capillary side?

Is this higher or lower inside the cell itself?

A

0.14M

Around the same on each side.

It’s much lower inside the cell.

27
Q

Why is the concentration inside the cell different to the concentration outside the cell in the lumen and capillary side?

A

To maintain a strong concentration gradient of sodium ions, between the outside of the cell and the inside of the cell.

28
Q

Explain the net movement of the potassium and sodium transport system? And how a membrane potential is generated?

A

Both potassium and sodium are positively charged (i.e. cations).

Because 2 potassium ions move one way and 3 sodium ions move in the opposite direction, there will be a net movement of 1 positive charge leaving the cell on each cycle.
Therefore the NaK ATPase will generate a membrane potential.

Creates an electrochemical gradient with low Na+ inside the cell.

29
Q

Which cation has the highest concentration in mammalian cells?

A

Potassium

Around 130-140mM

30
Q

What happens in the large intestine in terms of transport?

A

Chloride ions follows an electrochemical gradient, created by the sodium-potassium ATPase.

The ATPase pumps sodium out, creating a concentration gradient, from outside to inside the cell.

31
Q

What happens in the large intestine in terms of chloride and sodium channels?

A

Chloride and sodium channels are found on the Lumenal side.

The Epithelial Na+ channel (ENac) allows sodium to flow into the cell, down the concentration gradient.

Epithelial Na+ channel allows Lumenal Na+ ions to flow into the cell, down their electrochemical gradient; which creates an electrical potential across the Lumenal membrane

Chloride ions flow into the cell to neutralise this potential difference - This is a passive, uncoupled chloride channel.

32
Q

What happens in the small intestine in terms of transport?

A

Na+ /K+ ATPase, creates a sodium gradient.

Carbonic anhydrase is present inside and outside the cell, making carbonic acid (H2CO3) from carbon dioxide and water.

The sodium pump is able to pump potassium inside of the cell, to outside, so up its concentration gradient. This creates an electrochemical gradient.

There is a high concentration of bicarbonate ions because the protons are being removed.

So the bicarbonate ions want to flow down their gradient, to the outside of the cell.

So they pump chloride ions from outside to inside the cell.

33
Q

What is DRA?

What is NHE3?

A

DRA – Down-regulated in Adenoma protein

NHE3 – Sodium/Proton Exchanger 3

DRA and NH3 are a chloride-bicarbonate exchanger – which allows chloride to be pumped into the cell.

34
Q

What do NA+ need for transport in the SI?

A

Proton.

Na+ entry is coupled to proton (H+) efflux via coupled Na+/H+ antiport. The protons are provided by carbonic anhydrase.

35
Q

What is another function of Carbonic anhydrase in the small intestine?

A

Carbonic anhydrase also creates HCO3- ions

The HCO3- gradient drives Cl- uptake via another antiport; HCO3- flow out and Cl- are driven into the cell.

36
Q

Explain how Sodium is secreted?

A

The NA+ / K+ ATPase is driving NaCl secretion, as well as uptake.

It is driving NaCl via CFTR (Cystic Fibrosis Transmembrane regulatory protein).

The ATPase is coupled with NKCC1 (Na+/K+/2Cl- cotransporter protein).

The concentration gradient of sodium drives the uptake of potassium and 2 chloride ions.

This gives us a high concentration gradient of chloride ions in the cell.

These will naturally flow down their concentration gradient via the CTFR and sodium will follow across the junctions of the cell, via this paracellular sodium transport mechanism.

In this system, there is no Na+ channel in the Lumenal membrane – the sodium goes via the paracellular route.

Na+/K+ ATPase drives high cellular Cl- levels in the cell via the Na+/K+/2Cl- cotransporter – this is found on capillary membrane.

So sodium can only enter the cell from the capillary, from the blood.

So, Cl- flows out of the cell, into the lumen via CFTR – high Lumenal Cl- creates electrical potential.

This draws Na+ into lumen via this paracellular route.

37
Q

What are the three major carbohydrates?

A

Lactose
Starch
Sucrose

38
Q

Explain what enzymes break down these three major carbohydrates?

A

Lactose is broken down by Lactase.
It is broken down into galactose and glucose,

Starch is broken down by Amylase. It is digested into maltose, maltotriose and a-Limit dextrin.
These are then broken down by the enzyme a-glucosidases, to give us glucose.

Sucrose is broken down by Sucrase. It is broken down into glucose and fructose.

These products (glucose, fructose and galactose) are taken up by passing passively through the GLUT 5 transporter for fructose (this takes fructose down its conc gradient).

39
Q

Explain how these three major carbohydrates are absorbed?

A

The products (glucose, fructose and galactose) are taken up by passing passively through the GLUT 5 transporter for fructose (this takes fructose down its conc gradient).

OR

By the sodium-glucose transporter.

This uses a sodium gradient, which drives the uptake of glucose or galactose; and sucks every last bit of glucose out of the gut.

The na/k ATPase creates a sodium gradient from the outside of the cell to the inside of the cell.

This time, by transporting sodium across the capillary membrane.

40
Q

Where is SGLT1 found?

A

The SGLT1 (na+ - glucose transporter) is found on the lumneal surface.

41
Q

What enzymes break down polypeptides?

And are the products?

A

Polypeptides are broken down by pepsin, trypsin, chymotrypsin, elastase and carboxypeptidase A+B.

This gives us free amino acids (40%) or Oligopeptides (60%) which are short stretches of multiple amino acids.

42
Q

What happens to Oligopeptides?

A

Oligopeptides are further digested by endopeptidases, aminopeptidases and dipeptidases, to give us a good mixture of free amino acids and dipeptides and tripeptides.

There are specific transporters for all of these.

43
Q

Is the uptake of amino acids and peptides passive or active?

Why?

A

Active!

Because it is driven by the na/k ATPase, causing sodium ions down its gradient to transport amino acids, sometimes, up their gradient.

44
Q

Where is glucose actively transported to? And why?

A

Glucose is actively transported from the gut into the enterocyte, to ensure maximal uptake of glucose from digested food.

45
Q

What are GLUT transporters and where are they found?

A

GLUT transporters are passive transporters, that transport glucose.

Of the two sodium glucose transporters, SGLT1 is found in the enterocytes, and SGLT2 is found in the kidney.

46
Q

How does the enterocyte actively transport glucose into the cell?

A

The NaKATPase creates a low enterocyte Na+ concentration. The Na+ gradient stores energy which is used to cotransport glucose into the cell

47
Q

How are dipeptides transported into the enterocyte?

A

By a proton-dipeptide symport.

48
Q

Explain how lipids are absorbed?

A

Fat globules (lipids) mix with the bile salts and form emulsion droplets.

The outside of the droplets are the salts and the inside is the fat.

These fat globules are then broken down into smaller particles, resulting in an emulsion. This gives us a high SA:V ratio, which allows the lipase enzymes to work at the surface of the emulsion droplets.

This gives us a mixture of free fatty acids and monoglyceride.

These fatty acids form micelles.

These bind with bile salt to give us a high SA:V ratio, to keep them in solution.

At the brush boarder, these are taken up into the cell as free fatty acids.

Then they are reconstituted with glycerol to triglycerides, which are packed into chylomicrons.

These are transported into the lacteal, to be slowly released into the blood, avoiding the liver (first pass metabolism), then they are transported to adipose tissue, which fat is stored.

49
Q

Are long or short chain fatty acids soluble?

What does this mean?

A

Short chain fatty acids are soluble, meaning they can dissolve in water, so they go into the capillary system, where they can be metabolised in the liver.

50
Q

Explain plasma lipoproteins?

A

Plasma lipoproteins have a hydrophobic core of triacylglycerol and cholesterol esters.

51
Q

What are bile salts?

A

Bile salts are cholesterol derivatives secreted from the liver, into the intestine.

At high concentrations, they are toxic.
So instead of making a lot of them, they are recirculated between the liver and the intestine.

Secreted from liver in bile; form micelles in small intestine; reabsorbed in distal ileum

52
Q

How much bile salt is secreted?

A

20-30g of bile salts are secreted.

53
Q

Explain how bile salts are carried around / travel?

A

They travel down the intestine until all the fat has been removed, then they are deconjugated and are taken up by Apical Na+ - dependent bile acid transporter (they are a co-transporter) using sodium gradient so Na/k ATPase drives it.

Once in the cell, MRP3 (active process) and a co-transporter takes the Taurocholate (the bile acid) back into the blood and is transported back into the liver.

Na+ taurocholate co-transporting polypeptide allows it to be reabsorbed by the hepatocytes.

54
Q

What happens once Xenobiotics are in the body?

A

Xenobiotics are conjugated to glucuronic acid and excreted via biliary route, along with bile salts.

55
Q

Explain Enterohepatic recirculation for Xenobiotics?

What is the result of this?

A

Once free in the gut, they can be deconjugated from the beta-glucuronide and you get back to your free drugs (ROH), which is reabsorbed via the portal vein, and taken back to circulation.

These can delays the elimination of xenobiotics and can increase toxicity, because it increase plasma levels.

56
Q

The reabsorption of bile salts by enterocytes is an active process, carried out by the apical Na+ dependent bile acid transporter. In which part of the GI tract does this occur?

A

The distal (late) part of the ileum.

57
Q

Why are bile acids an important role in fat digestion?

A

Helps to emulsify fat particles into many minute particles so the surfaces can then be attacked by lipase enzymes of pancreatic juice.