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ICPP > ICPP 3 Intracellular pH + Cell Volume Control > Flashcards

ICPP 3 Intracellular pH + Cell Volume Control Flashcards

1
Q

Cytoplasmic pH

A

7.2

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2
Q

Why does intracellular pH vary depending on the organelle?

A

pH relates to function

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3
Q

Normal pH range

A

7.35-7.45

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4
Q

Acidosis range

A

7-7.35

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5
Q

alkalosis range

A

7.45-7.8

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6
Q

Relationship between [H+] and pH

A

Change in [H+] by a factor of 2 causes a pH change of 0.3

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7
Q

Reasons for tight pH regulation

A
  • disrupts electrostatic interaction + H bonding
    (doesn’t effect covalent)
  • alters protein structure and function
  • alters binding of substrate and ligands
  • alters net electrical charge on proteins
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8
Q

Intracellular pH dysregulation and tissue ischaemia

A
  • Reduced blood flow > reduced O2 supply > anaerobic glycolysis > lactic acid > cytoplasmic acidification
  • overactivation of NHE > intracellular Na overload > Ca overload via NCE
  • leads to altered cellular function, apoptosis + necrosis
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9
Q

What is Dents disease characterised by?

A

Proximal tubule dysfunction > progressive renal failure

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10
Q

What is Dens disease due to?

A

Mutations in CLC5 (2Cl-/H+ exchanger)
Defective endocytosis due to impaired acidification

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11
Q

What does the electrochemical gradient favour?

A

Inward movement of H+
Outward movement of HCO3 -

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12
Q

Role of buffers

A

Immobilise H+
Reduced destructive effects
Insufficient on their own

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13
Q

3 primary buffer systems

A

Bicarbonate buffer system
Phosphate butter system
Proteins

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14
Q

Bicarbonate buffer system

A

CO2 + H2O <> H2CO3 <> H+ + HCO3 -

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15
Q

How do proteins act as buffers?

A

Contain many H+ binding sites

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16
Q

Phosphate buffer system

A

H+ + PO^4 2- <> H2PO^4 -

17
Q

NHE meaning

A

Na+/H+ exchanger

18
Q

How does the NHE control cell pH?

A

1 H+ out
Na+ in

19
Q

What is NHE activated by?

A

Growth factors

20
Q

What is NHE inhibited by?

A

Amiloride

21
Q

How does the sodium bicarbonate chloride cotransporter control cell pH?

A

1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out

22
Q

How does the sodium bicarbonate chloride cotransporter control cell pH?

A

1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out

23
Q

NBC meaning

A

Sodium bicarbonate chloride cotransporter

24
Q

How doe NBC control cell pH?

A

1 Na+ in
1 H+ out
1 HCO3 - in
1 Cl- out

25
Q

AE meaning

A

Anion exchanger
Cl/HCO3 - exchanger

26
Q

What is the AE dependent on?

A

The conc of the ions its transporting

27
Q

What type of transporters are NHE and NBC and what are the dependent on?

A

Secondary
Facilitated diffusion
Dependent on Na+ electrochemical gradient set by the Na+ K+ pump

28
Q

What pH does NHE work best at?

A

Low pH
H+ out > alkalises cell

29
Q

What pH does AE2 work better at?

A

High pH
Acidifies cell

30
Q

Why does cell volume need to be regulated?

A
  • Excessive swelling jeopardises membrane integrity
  • Swelling and shrinking interferes with cytoskeleton
  • Cell function dependent on correct protein hydration
31
Q

Hypernatremic meaning

A

High Na+ blood conc

32
Q

Hyponatremic meaning

A

Low Na+ blood conc

33
Q

Relationship of solutes and water

A
  • water follows solutes
  • net influx of solutes > net influx of water > cell swelling
  • net efflux of solutes > net efflux of water > cell shrinkage
34
Q

Acid extruders

A

NHE - efflux of H+&raquo_space; alkalisation of cell
Sodium bicarbonate cotransporter - coupled with Cl- > alkalisation by removing H+ and adding HCO^3 -

35
Q

Base extruders

A

Cl-/HCO^3 - exchanger (anion exchanger) - acidifies cell

36
Q

Mechanisms to resist cell swelling

A
  • conductive systems
  • cotransport systems

Efflux of osmotically active solutes K+ or Cl-&raquo_space; water follows&raquo_space; reduced cell swelling

regulatory volume decreases

37
Q

Mechanisms to resist cell shrinking

A
  • conductive systems
  • cotransport systems

Influx of osmotically active ions Na+, K+ or Cl-&raquo_space; water follows in&raquo_space; reduces cell shrinking

Regulatory volume increase

NHE
SBC - sodium bicarbonate chloride cotransporter

38
Q

Longer term changes to resist cell swelling

A

Amino acids efflux > H2O follows > reduced cell swelling

39
Q

Longer term changes to resist cell shrinkage

A

Synthesis or transport of organic solute
e.g. sorbitol, inositol - sugars
taurine, betaine - amines

ICPP (18 decks)

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