Buffer

A buffer is a solution containing substances which have the ability to minimise changes in pH when an acid or base is added to it.

Buffer systems in human body
[1] The major buffer system in the Extracellular Fluid is the CO2-bicarbonate buffer system.
This is responsible for about 80% of extracellular buffering.
It is the most important ECF buffer for metabolic acids but it cannot buffer respiratory acid-base disorders.

Then which buffer is responsible for buffering respiratory acid- base disorders ?

[2] The other buffer systems in the blood are the protein and phosphate buffer systems.
These are the only blood buffer systems capable of buffering respiratory acid-base disturbances as the bicarbonate system is ineffective in buffering changes in H+ produced by itself.

Among proteins and phosphates which one more important?

[3] The phosphate buffer system is NOT an important blood buffer as its concentration is too low.

[4] Protein buffers in blood include haemoglobin (150g/l) and plasma proteins (70g/l).
Buffering is by the imidazole group of the histidine residues which has a pKa of about 6.8. This is suitable for effective buffering at physiological pH.
Haemoglobin is quantitatively about 6 times more important then the plasma proteins as it is present in about twice the concentration and contains about three times the number of histidine residues per molecule.

Note :Deoxyhaemoglobin is a better buffer than oxyhaemoglobin.

[6] Respiratory acid base imbalance  are predominantly buffered in the intracellular compartment.
Metabolic disorders have a larger buffering contribution from the extracellular fluid.

Note : It has been estimated that at least 40% of the buffering of an acute acid load takes place in bone. Chronic acidosis can have very adverse effects on bone mineralization due to this process and can result in bone diseases such as rickets, osteomalacia and osteopenia.

So to summarise :
Major ECF Buffer = Bicarbonate system
Major ISF buffer = Bicarbonate system
Major Blood buffer = Bicarbonate system (overall)
Major Blood buffer for respiratory acid base imbalence = Hb
Major ICF Buffer = Protein buffer> phosphate buffer
Major buffer in urine = Phosphate (Responsible for most of 'Titratable Acidity')