Cell Processes: Traffic across epithelial cells: chloride secretion Flashcards

1
Q

What is a NaK2Cl symporter

A

Transporter that uses the energy of the Na gradient to actively accumulate chloride above its electrochemical gradient (in chloride secretion)

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2
Q

How does Cl leave cell in chloride secretion?

A

Cl leaves the cell by passive diffusion through an ion channel (exit step = secretion) it is selective for Cl- and gated (regulated)

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3
Q

Why and how does Na and K leave cell in chloride secretion

A

Na exits via the basolateral Na-pump and K + via channel (K leaving makes cell more negative, so Cl- will want to leave negative environment)

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4
Q

What does the transport of Cl across the epithlium do?

A

induces paracellular Na and water fluxes (creates negative environment which attracts positive ions)

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5
Q

What is the rate limiting step of chloride secretion

A

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) (channel shut = no Cl- movement, no isotonic secretion)

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6
Q

What causes secretory diarrhoea?

A

Caused by excessive stimulation of the secretory cells in the crypts of the small intestine and colon
Cells become over stimulated pump out a lot of Cl- so a lot of Na and water (exceeding capacity to reabsorb fluid in gut)

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7
Q

One possible cause of excessive stimulation of the secretory cells. These molecules are produced by tumours and inflammation.

A

abnormally high concentrations of endogenous secretagogues

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8
Q

What are the crypts

A

Location of secretory cells in the small intestine and colon

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9
Q

A cause of excessive stimulation of the secretory cells due contaminated water

A

secretion of enterotoxins from bacteria such as Vibrio cholerae

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10
Q

What are enterotoxins

A

toxins that irreversibly activate adenylyl cyclase causing a maximal stimulation of CFTR lead to a secretion that overwhelms the absorptive capacity of the colon

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11
Q

What does oral therapy treat?

A

secretory diarrhoea caused by cholera

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12
Q

5 step cholera toxin mechanism

A

cholera toxin irreversibly acts on adenylyl cyclase -> excess cAMP produced -> protein kinase A phosphorylates R region of CFTR -> ATP binds to nucleotide binding domain -> CFTR channel stays open

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13
Q

What are villus cells involved in?

A

Absorption

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14
Q

What is cystic fibrosis

A

A genetic disorder affecting children and young adults, usually ending in death from respiratory issues.

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15
Q

How is cystic fibrosis inherited

A

It is inherited in an autosomal recessive fashion (Heterozygotes have no symptoms but are carriers)

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16
Q

Likelihood of a child from two carriers getting cystic fibrosis

A

1/4

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17
Q

Proportion of Northern European newborns affected by CF

A

1 in 2500

18
Q

Proportion of Northern Europeans who are carriers of CF

A

1 in 25

19
Q

6 organs commonly affected by CF

A

Airways, liver, pancreas, small intestine, reproductive tract, skin

20
Q

4 treatments to manage CF and increase survival time

A

chest percussion, antibiotics, enzyme replacement, attention to nutrition

21
Q

Most common way cystic fibrosis kills people

A

respiratory failure

22
Q

Median survival of patients with CF

A

38 years

23
Q

What does CFTR stand for

A

Cystic fibrosis transmembrane conductance regulator

24
Q

What is CFTR

A

Cl channel regulated by protein kinase A dependent phosphorylation of the R domain and binding of ATP to the NBD (nucleotide-binding domain)

25
Q

What causes R domain to leave CFTR pore

A

Binding of ATP to cause R domain to leave pore

26
Q

The absence of functional CFTR receptors in the lungs creates a

A

dry lung surface

27
Q

CFTR lung pathology (7)

A

CFTR gene defect -> defective ion transport -> airway surface liquid depletion -> defective mucociliary clearance -> mucus obstruction, infection, inflammation

28
Q

What does a normal lung epithelial cell do in Cl secretion

A

it has a balance between secretion and absorption keeping the lung surface moist and prevents excessive fluid build up

29
Q

What does a lung epithelial cell do in CF

A

the defective Cl- channel prevents isotonic fluid secretion and enhances Na+ absorption to give a dry lung surface

30
Q

Two stages of sweat formation

A

Primary isotonic secretion of fluid (by acinar cells), secondary reabsorption of NaCl to produce a hypotonic solution (by duct cells)

31
Q

What does failure to reabsorb NaCl in ducts of sweat glands do?

A

produce salty sweat in CF patients

32
Q

Neurotransmitters that stimulate sweat production

A

ACh (Acetylcholine), NA (Noradrenaline)

33
Q

Parasympathetic stimulation of sweat production uses…

A

ACh

34
Q

Sympathetic stimulation of sweat production uses…

A

NA

35
Q

What is CLCA

A

Chloride channel accessory, controlled by calcium - in Acini, controls secretion of Cl-

36
Q

What is ACh

A

Neurotransmitter that activates CLCA

37
Q

What is NA

A

Neurotransmitter that activates CFTR

38
Q

What is ENaC

A

Epithelial sodium channel, responsible for reabsorbing sodium out of the sweat.

39
Q

What special about CFTR

A

It is the only chloride channel responsible for reabsorbing chloride from sweat

40
Q

in sweat formation, why do Cl want to enter cell down electrochemical gradient

A

duct cells the membrane potential is depolarised

41
Q

Where does Cl- accumulate in CF patients

A

Cl- accumulates in the duct lumen producing salty sweat