Maintenance of pH

Question 1

What is the range of pH values?

Answer 1

Biological fluids range from pH 1 to pH 9.
Most physiological processes within cells occur in the range pH 5 - pH 7.6

Question 2

How is pH measured?

Answer 2

Litmus paper
pH meter

Question 3

What are different pH values around the body?

Answer 3

Stomach - pH 2
Plasma - pH 7.4
Pancreatic juice - pH 8.8

Question 4

What are strategies for pH regulation?

Answer 4

Partitioning
Buffering

Question 5

What is partitioning?

Answer 5

Adding a proton pump, which moves protons into intermembrane space.
Protons can’t cross membranes alone.
This increases pH.

Question 6

What is used to regulate pH in the blood?

Answer 6

Partitioning cannot be used as blood needs tightly monitoring.
So buffers are used.

Question 7

What is carbonic acid?

Answer 7

Major buffer of the body - acts in circulation and in tissues.
CO2 + H2O <–> H2CO3 <–> HCO3- + H+
H2CO3 is carbonic acid
HCO3- is bicarbonate ion.

Question 8

What is carbonic anhydrase?

Answer 8

The binding of CO2 from the blood with water to form carbonic acid is very slow so carbonic anhydrase speeds this up.

Question 9

Where is gastric acid made?

Answer 9

In parietal cells in gastric glands of the stomach.

Question 10

How is gastric acid made?

Answer 10

CO2 is taken from the blood and carbonic anhydrase converts it into carbonic acid.
Carbonic acid dissociates into bicarbonate ion and a proton.
The HCO3- ion is antiported back into the blood stream against Cl- going into the cell.
The proton and Cl- is antiported into the gastric duct with a potassium ion going into the cell then the blood.

Question 11

Why is the process of creating gastric acid important?

Answer 11

It creates bicarbonate in the blood, which keeps equilibrium on the right hand side.
H2CO3 <–> HCO3- + H+
Chloric acid is also created in the stomach

Question 12

Why is it important for blood pH to be controlled?

Answer 12

Under strenuous conditions pH falls to 6.8, and this is not sustainable for long before a coma or death occurs.
pH can also increase to 7.8, which leads to dissociation of side chains to produce protons.

Question 13

What is an example of pH being too high?

Answer 13

At 7.8, the protein albumin dissociates from its side chains and becomes negative.
The negative charge captures Ca2+, so extracellular Ca2+ falls, leading to tetanic cramps.

Question 14

What is acidosis?

Answer 14

Blood pH below 7.35, normal pH is 7.4
[HCO3-] is a lot less at pH 7.03 compared to 7.4, and so the buffering capacity is greatly reduced.

Question 15

What is the response to alteration of acid-base balance?

Answer 15

1st defence - buffering
2nd - alteration in arterial pCO2
3rd - alteration in HCO3- excretion

Question 16

How does pKa affect drug uptake?

Answer 16

pKa dictates the fluid in which to administer drug and the volume administered.
This influences the concentration of ionised and unionised drug in solution and whether the drug will remain in solution or precipitate.

Question 17

How are weak acids or weak base drugs influenced?

Answer 17

These drugs are actively secreted into the renal tubule and so rapidly excreted.

Question 18

How does benzoic acid act?

Answer 18

In high proton concentration like in the stomach most of the drug is protonated, so can be taken up by the cells and enter the blood stream.
The blood stream has a pH of 7.4 so the uncharged form dissociates mainly into the ionic form.
So whatever enters the blood is locked inside the plasma.

Question 19

How does phenylamine act?

Answer 19

Mostly protonated because it is a basic compound so the ionic form is in gastric juice so can easily leave the plasma as most of it is uncharged and can diffuse back.

Question 20

How do you calculate the stability of salt bridges in proteins?

Answer 20

Calculate the pH range where more than 50% of the protein is in its charged form, using the Henderson Hasslebach equation.

Question 21

Why is there a high pH in the nucleus?

Answer 21

DNA is acidic, but the pH in the nucleus is basic.
DNA is not the only molecule in the nucleus - histone are basic proteins with positive charges.
DNA is wound round histones so it is tightly packed, to prevent the negative charges in the phosphate backbone elongating.

Question 22

Why is the pH in lysosomes 5.5?

Answer 22

Lysosomes are slightly acidic because the enzymes digest the proteins - which is more effective in an acidic environment, so lysosomes are filled with acidic molecules.

Question 23

Why is there a difference in pH across the mitochondrial membrane?

Answer 23

6.8 in matrix vs 7.8. in membrane.
Intermembrane space has more protons than in matrix.
Energy rich electrons are donated to Electron Transport Chain then to electron centre, losing energy, so proton is pumped from matrix into intermembrane so proton gradient is established.