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ICPP > Lecture 5 - Intracellular PH And Cellular Volume > Flashcards

Lecture 5 - Intracellular PH And Cellular Volume Flashcards

1
Q

What is normal plasma/serum pH?

A

7.35 - 7.45

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2
Q

What are the 2 major organs responsible for maintain acid base balance?

A

Lungs-Respiratory balance
Kidneys-Metabolic balance

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3
Q

What is the pH limits of human tissue survival?

A

6.8 - 7.8

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4
Q

If the concentration of H+ doubles how much does the pH change?

A

Decreases by 0.3

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5
Q

Why is it so important for pH to be regulated tightly?

A

Can change electrical charge on proteins
Disrupt electrostatic interactions, hydrogen bonds
Altering protein structure and function
May change structure of binding sites for substrates

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6
Q

What is normal cytoplasmic pH?

A

7.2

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7
Q

Why do lysosomes and endosomes have an acidic pH?

A

Important in degradation of proteins and recycling of receptors

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8
Q

What is the significance of cytoplasmic pH being lower than plasma pH?

A

There’s a concentration gradient between the cell and the plasma giving H+ the drive to move out of the cell

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9
Q

How does tissue ischaemia lead to cytoplasmic pH dysregulation?

A

Reduced blood flow = reduced O2 to cells
Reduced O2 = increased anaerobic glycolysis = more lactic acid = higher [H+] in the cell

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10
Q

How does the cell becoming more acidic in tissue ischaemia lead to altered cell function or apoptosis?

A

Increased [H+] = over activation of Na+/H+ exchanger (NHE)
Leads to Na+ overload/influx
Na+/Ca2+ exchanger activated
Overload of Ca2+
Ca2+ activates unwanted enzymes
Caspases activated = apoptosis

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11
Q

What is Dents disease?

A

Proximal tubule dysfunction and progressive renal failure

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12
Q

What causes Dents disease?

A

Mutated Chloride proton exchanger + defective endocytosis due to impaired acidification

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13
Q

Normally, which way is the electrochemical gradient across the membrane of a (polarised) cell compared to the blood?

A

Cells usually more negative inside
Extracellular usually more positive

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14
Q

What is the main cause of intracellular pH decreasing (acidification)?

A

Electrochemical gradient
(H+ favoured to move into more negative cell and HCO3- more likely to move out)

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15
Q

During metabolism which molecule usually lead to production of protons and what is this equilibrium reaction?

A

CO2

CO2 + H2O ——- H2CO3
H2CO3 ——- H+ + HCO3-

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16
Q

What are the 3 buffer systems regulating intracellular pH?

A

Bicarbonate buffer system (Most important)

Phosphate buffer system

Proteins

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17
Q

What needs to accompany buffer systems to regualte intracellular pH?

A

Dynamically regulated transport processes

18
Q

What are some important acid extrudes essential in regulating intracellular pH?

A

NHE (Na+/H+ exchanger)

Na+ dependant Cl-/HCO3- exchanger

19
Q

How does NHE affect cell pH?

A

Secondary active transporter
Na+ moves into cell H+ moves out of cell

Alkalinises the cell

20
Q

How does a Na+ dependant Cl-/HCO3- exchanger affect cellular pH?

A

Na+ transports HCO3- into cell
Cl- with some H+ removed from cell

Removal of HCO3- reduces [H+] in cell as well as removing H+

21
Q

What is an example of a base extruder?

A

Cl-/HCO3- exchanger (an AE anion exchanger)

22
Q

How does an AE act as a base extruder regulating cellular pH?

A

HCO3- released from cell, Cl- brought into cell

Decreasing Intracellular [HCO3-] shifts equilibrium increasing [H+]
Acidification of cell

23
Q

Which 3 exchangers/cotransporters are important in regulating cell volume?

A

NHE (Na+/H+ exchanger)
NBC (Na+ bicarbonate chloride cotransporter
AE (HCO3- / Cl- exchanger)

24
Q

Which transporter is important in ensuring extracellular [Na+] is greater than intracellular?

A

Na+/K+ ATPase (Sodium pump)

Maintains Na+ gradient to provide energy for secondary/tertiary active transporters

25
Q

Why is an AE not a secondary transporter?

A

Not determined by the concentration of Na+

26
Q

In terms of activity how does the activity of NHE and NBC change as Intracellular pH becomes more acidic?

A

NHE activity increases
NBC activity increases (sodium bicarbonate transporter) (moves Na+ and HCO3- into the cell)

27
Q

What is the function of NHE?

A

Brings Na+ into cell
Pumps H+ out of cell

28
Q

What is the role of NBC?

A

Brings Na+ and HCO3- into cell
Pumps H+ and Cl- out of cell

29
Q

What is the role of AE?

A

Brings Cl- into cell
Pumps HCO3- out of cell

30
Q

Why are NHE and AE very sensitive to pH changes?

A

PH must be maintained tightly

31
Q

How does the activity of NHE, NBC and AE change as pH gets more alkaline?

A

NHE decreases
NBC decreases
AE increases

32
Q

Why does a cell need to be able to regulate its volume?

A

Excess swelling = jeopardises membrane integrity

Shrinking and swelling = cytoskeleton interfered with

Proteins need correct hydration

33
Q

What is meant by a cell being in a hypertonic solution?

A

Solution osmolarity high
More water in cell moves out, cell shrinks

34
Q

What is cell shrinkage called?

A

Plasmolysis

35
Q

What is a hypotonic solution?

A

Solution osmolarity lower than cell
Water moves into cell, cell swells

36
Q

Why is hypernatremia and hyponatremia dangerous?

A

Changes in plasma osmolarity lead to cell shrinkage or swelling

37
Q

What happens to water when solutes leave a cell?

A

Water follows and moves out

38
Q

What are the cells mechanisms for a cell to resist swelling (carrying out Regulatory Volume Decrease? (acute response)

A

Osmotically active ions effluxed (water follows)

K+ stretch activated channels
Cl- Stretch activated channels
K+/Cl- Co-transporter

39
Q

What are the cells mechanisms for a cell to resist shrinking (carrying out Regulatory Volume Increase? (acute respone)

A

Osmotically active particles influxed

Na+/Cl- cotransporter
Na+/K+ 2Cl- cotransporter
NHE may be activated removing H+ bringing Na+ in

40
Q

How does synthesis of organic solutes help prevent cell shrinkage? (Chronic response)

A

Increases solute concentration in the cell
Water moves into cell

41
Q

What is the chronic response to resistaning swelling (regulatory volume decrease)?

A

Efflux and reduced synthesis of organic osmolytes (glucose)

ICPP (23 decks)

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