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biosci S1 Pt2 > Lec 18 - Transport of chloride > Flashcards

Lec 18 - Transport of chloride Flashcards

1
Q

What is the mechanism of chloride secretion?

A
  1. Na pump sets up ion gradients
  2. The NaK2Cl symporter brings in Cl
  3. The Cl exits by passive diffusion through an ion channel
  4. Na leaves via NaKATPase, and K leaves via the K channel
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2
Q

What type of transporter is the NaK2Cl symporter?

A

Secondary active transporter

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3
Q

How does the NaK2Cl symporter bring Cl into the cell?

A

By bringing in Na+ down its electrochemical gradient, it brings in Cl- and K+ against their electrochemical gradients, and using the energy stored in the Na gradient

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4
Q

How many of each ion are brought into the cell by the NaK2Cl symporter?

A

Its in the name- one Na, one K and 2Cl

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5
Q

What makes a transporter a symporter?

A

If everything moving across it is going in the same direction

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6
Q

Why will chloride have to move out of the cell once it enters?

A

because adding more would be electrically unfavorable, so more has to leave before other ones can enter.

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7
Q

What will happen in terms of electroneutrality?

A

Because the Cl ion is moved across the cell, it will attract a counter ion (Na+) and water via the paracellular membrane

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8
Q

Cells in our body should always be…? (tonicity)

A

Isotonic (which is why electroneutrality and osmosis exist)

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9
Q

What is the rate limiting step of chloride secretion?

A

The opening of the Cl- ion channel, which is strictly gated

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10
Q

What has the Cl- channel been identified as at the molecular level?

A

Cystic fibrosis transmembrane conductance regulator (CFTR)

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11
Q

What percentage of people have CFTRs?

A

100%. it is only when it is not properly functioning that it causes cystic fibrosis

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12
Q

What causes secretory diarrhea?

A
  • ## excessive stimulation of the secretory cells in the crypts of the small intestine
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13
Q

what can cause excessive stimulation in secretory cells?

A

Abnormally high concentration of secretagogues caused by tumor or inflammation

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14
Q

what do secretagogues do?

A

They are hormones that stimulate pathways that open the CFTR channels to start secretion

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15
Q

What is secretory diarrhea more commonly due to?

A

the secretion of enterotoxins from bacteria such as cholerae

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16
Q

what do enterotoxins do?

A

irreverisbly active adenylate cyclase, causing a maximal stimulation of ctfr. This then leads to a secretion that overwhelms the absorptive capacity of the colon(cAMP)

17
Q

What happens in the normal process of secretion at the molecular level?

A

Secretogogue binds to GPCR in the basolateral membrane. This causes a molecule to activate adenylate cyclase, which converts ATP to cAMP. Then protein kinase A phosphorylates CTFR and the gate opens in the apical membrane.

18
Q

How does cholera effect the process of secretion at the molecular level?

A

It binds to the active site of adenylate cyclase and causes the stimulation

19
Q

explain the mechanism here

A

Cells are being renewed at the crypt (where secretion happens), and as they get older they move towards the villus (where absorption happens). Therefore their gene expression changes.

20
Q

How can we treat secretory diarrhea caused by cholera?

A

oral rehydration therapy- due to constantly renewing cells in the small intestine we could just wait for those cells to renew after 5 days ish

21
Q

is cystic fibrosis inherited?

A

yes, in autosomal recessive fashion (so heterozygotes won’t have it but will be carriers) Therefore a child of two carriers have a 1 in 4 chance

22
Q

how does disease frequency vary among ethnic groups?

A

high in northern europe, but low around asian and african ethnic groups

23
Q

What organs are effected by cystic fibrosis?

A

Airways
reproductive tract
liver
pancreas
small intestine
skin

24
Q

What type of tissue is most involved in cystic fibrosis?

A

epithelial tissues

25
Q

List the four clinical management options for cystic fibrosis

A

chest percussions to improve clearance of infected secretions
antibiotics for infections
pancreatic enzyme replacement
attention to nutritional status (diet to prevent colon blockage)

26
Q

What is the median survival time for cystic fibrosis?

A

38 years (increased since he wrote that)

27
Q

Is the CTFR a primary active transporter? If so, why?

A

Yes, because it has sites attached which bind and hydrolyse ATP

28
Q

Is the CTFR a channel?

A

yes

29
Q

Describe the process of the CTFR channel opening

A

Protein kinase A phosphorylates the R domain. THEN atp can bind to their sites (NBD - nucleotide binding domain).

30
Q

What is the energy consumption step when opening the CTFR channel?

A

Opening of the channel uses atp, the ions are not being pumped so not that.

31
Q

Why do we want a moist surface of cells in the lungs that are absorbing oxygen?

A

because the oxygen needs to be dissolved close to the cell

32
Q

How does moisture (water) accumulate on cell surfaces in the lungs?

A
  • Ion gradient set up (NaKATPase)
  • chloride accumulates above chemical equilibrium
  • CFTR opens and chloride exits to apical surface
  • movement of Na+ (counter ion) and water follows.
33
Q

Does water sit on the surface of cells?

A

no, there is a balance between secretion absorption, which keeps the lung surface moist but prevents excessive fluid build-up (Na+ and Cl- movement)

34
Q

What happens to cells of the lungs in people who have cystic fibrosis? (think water)

A

the CFTR doesn’t work, so there is not chloride secretion, but there still is Na+ absorption, and due to osmosis there is water movement and so lungs get dehydrated.

35
Q

How is the mucus on the lung cells of people with cystic fibrosis affected?

A

The mucus builds up and sticks due to cell surface dehydration and it becomes a place for bacteria to aggregate rather than be removed.

36
Q

Why is sweat considered a hypotonic solution?

A

Because it has a lower salt concentration compared to our other body fluids

37
Q

why do people with cystic fibrosis have salty sweat?

A

Because of the defect to the CFTR channel, there is no absorption of Cl-, and therefore no movement of Na+ as a counter ion. so no sodium reabsorption in the second stage of sweat formation

biosci S1 Pt2 (16 decks)

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