Lecture 5 - Intracellular PH And Cellular Volume Flashcards
What is normal plasma/serum pH?
7.35 - 7.45
What are the 2 major organs responsible for maintain acid base balance?
Lungs-Respiratory balance
Kidneys-Metabolic balance
What is the pH limits of human tissue survival?
6.8 - 7.8
If the concentration of H+ doubles how much does the pH change?
Decreases by 0.3
Why is it so important for pH to be regulated tightly?
Can change electrical charge on proteins
Disrupt electrostatic interactions, hydrogen bonds
Altering protein structure and function
May change structure of binding sites for substrates
What is normal cytoplasmic pH?
7.2
Why do lysosomes and endosomes have an acidic pH?
Important in degradation of proteins and recycling of receptors
What is the significance of cytoplasmic pH being lower than plasma pH?
There’s a concentration gradient between the cell and the plasma giving H+ the drive to move out of the cell
How does tissue ischaemia lead to cytoplasmic pH dysregulation?
Reduced blood flow = reduced O2 to cells
Reduced O2 = increased anaerobic glycolysis = more lactic acid = higher [H+] in the cell
How does the cell becoming more acidic in tissue ischaemia lead to altered cell function or apoptosis?
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
What is Dents disease?
Proximal tubule dysfunction and progressive renal failure
What causes Dents disease?
Mutated Chloride proton exchanger + defective endocytosis due to impaired acidification
Normally, which way is the electrochemical gradient across the membrane of a (polarised) cell compared to the blood?
Cells usually more negative inside
Extracellular usually more positive
What is the main cause of intracellular pH decreasing (acidification)?
Electrochemical gradient
(H+ favoured to move into more negative cell and HCO3- more likely to move out)
During metabolism which molecule usually lead to production of protons and what is this equilibrium reaction?
CO2
CO2 + H2O ——- H2CO3
H2CO3 ——- H+ + HCO3-
What are the 3 buffer systems regulating intracellular pH?
Bicarbonate buffer system (Most important)
Phosphate buffer system
Proteins
What needs to accompany buffer systems to regualte intracellular pH?
Dynamically regulated transport processes
What are some important acid extrudes essential in regulating intracellular pH?
NHE (Na+/H+ exchanger)
Na+ dependant Cl-/HCO3- exchanger
How does NHE affect cell pH?
Secondary active transporter
Na+ moves into cell H+ moves out of cell
Alkalinises the cell
How does a Na+ dependant Cl-/HCO3- exchanger affect cellular pH?
Na+ transports HCO3- into cell
Cl- with some H+ removed from cell
Removal of HCO3- reduces [H+] in cell as well as removing H+
What is an example of a base extruder?
Cl-/HCO3- exchanger (an AE anion exchanger)
How does an AE act as a base extruder regulating cellular pH?
HCO3- released from cell, Cl- brought into cell
Decreasing Intracellular [HCO3-] shifts equilibrium increasing [H+]
Acidification of cell
Which 3 exchangers/cotransporters are important in regulating cell volume?
NHE (Na+/H+ exchanger)
NBC (Na+ bicarbonate chloride cotransporter
AE (HCO3- / Cl- exchanger)
Which transporter is important in ensuring extracellular [Na+] is greater than intracellular?
Na+/K+ ATPase (Sodium pump)
Maintains Na+ gradient to provide energy for secondary/tertiary active transporters
