Buffers, Need for Buffering, and Buffering Mechanisms

I. BUFFERS

1. Buffers are chemical substance systems found in blood and urine
2. Buffers are found in two compartments - ECF (extracellular fluid) and ICF (intracellular fluid)
3. ECF is plasma and blood. ICF is interstitial fluid (in between cells) and intracellular fluid (inside cells)
4. ECF buffers are carbonic acid-bicarbonate buffer system (maximal, most effective) and protein buffer systems. The phosphate buffer system is very minimal.
5. ICF buffers are phosphate buffer system, ammonia buffer system, and protein buffer systems

A. BLOOD BUFFERS

1. Blood is ECF
2. Bloof buffers are carbonic acid-bicarbonate buffer system and protein buffer systems
3. Phosphate buffer system buffers best as pH 7.4 but there is very little (limited amount) phosphate in blood to do this. So the phosphate buffer system plays a very minimal role in buffering blood pH even though it is the best buffer for the body.
4. Carbonic acid-bicarbonate buffer system plays a major role in buffering blood pH as there is plenty of it in blood, even though it buffers best at pH 6.1.
5. Proteins in blood plasma also buffer blood pH to a large extent since there is a lot of proteins in blood (60g-70g/L) but proteins are compartmentalised and due to their sizes, cannot easily or freely traverse cell membranes are well as bicarbonate can. Therefore, buffering is limited as well as compartmentalised.

1. CARBONIC ACID-BICARBONATE BUFFER SYSTEM

1. Carbonic acid-bicarbonate buffer system is most important in ECF
2. Carbonic acid-bicarbonate buffer system is volatile - carbon dioxide is expired or inhaled
3. In tissues, 93% CO2 enters rbc's. From this, 23% binds to Hb as carboxyHb while 70% forms carbonic acid which instantly dissociates to free bicarbonate and proton; proton binds to Hb to form protonated Hb (H.Hb) while potassium dissociates from Hb; bicarbonate then enters blood while chloride enters rbc's ("chloride shift"); chloride then associates with potassium in rbc's 
4. Approximately 70% of carbon dioxide is carried in the blood as bicarbonate
5. In the lungs, the reverse occurs in rbc's: bicarbonate enters rbc's while chloride exits rbc's ("chloride shift"); proton dissociates from H.Hb and combines with bicarbonate while potassium dissociate from chloride and recombines with Hb to form K.Hb; carbonic acid that is formed dissociates to CO2 and water; CO2 diffuses out of rbc's and is expired via alveoli in the lungs

2. PROTEIN BUFFER SYSTEMS

1. Protein buffer systems are found in both ECF and ICF
2. Protein buffer systems are: hemoglobin buffer system (in rbc's), amino acid buffers (all proteins), and plasma protein buffers. Plasma proteins are mainly albumin, transferin, antibodies, haptoglobin, etc. Plasma proteins are present as salt-weak acid systems and act as buffers in blood. The plasma protein buffering effect is minor compared to the bicarbonate system or hemoglobin system. The plasma protein buffering capacity is approximately one-sixth that of Hb
3. Protein buffer systems help to regulate pH in ECF and ICF
4. Protein buffer systems interact extensively with other buffer systems
5. The most powerful, plentiful buffer system in the body is the proteins of plasma and cells

B. URINARY BUFFERS

1. The body secretes hydrogen ions into the lumen of renal tubules
2. These secreted hydrogen ions either combine with phosphate of ammonia and are then excreted out of the body in urine. 
3. In acidosis, more hydrogen ions are excreted in urine in order to increase blood pH towards normal. Bicarbonate is reabsorbed and also regenerated.
4. In alkalosis, hydrogen ions are recaptured and returned to blood in order to reduce blood pH toward normal

1. PHOSPHATE BUFFER SYSTEM

1. Phosphate buffer system buffers pH of ICF and urine
2. There is minimal buffering by phosphate buffer system in blood. The phosphate buffers in the blood are inorganic phosphates
3. Phosphate buffer system is the main buffer in renal system
4. Intracellular buffers are both inorganic and organic phosphates
5. ICF phosphate buffer system consists of the anion monophosphate H2PO4- (a weak acid) and the anion biphosphate HPO42- (a base)

2. AMMONIA BUFFER SYSTEM

1. Tubular deamination of amino acids creates ammonia (NH3)
2. Ammonia freely diffuses into the renal tubule 
3. In the renal tubule, ammonia combines with proton to form ammonium (NH4+)
4. Ammonia is impermeable to the renal cell membrane and is not reabsorbed by the renal tubular cells but excreted
5. Hyperammonianemia is toxic to the brain and occurs in newborns with kidney problems.

II. NEED FOR BUFFERING

1. The body needs to keep its body fluids within a narrow range of pH as large fluctuations in pH are not compatible with life.
2. Extreme pH values are not compatible with life
3. Death occurs at extreme pH values: when pH < 6.80; when pH > 7.80
4. Life is only possible between a narrow pH range, between pH 6.80-pH 7.80 ... ie only 1 pH unit
5. Almost all the chemical reactions in our body are catalysed by enzymes. Enzyme activity is dependent on pH, between pH 6.80 and pH 7.80 (ie, physiological pH). Only a few enzymes are active at extreme pH.

III. BUFFERING MECHANISMS

1. Chemical buffers are immediate responders to any change in pH of body fluids
2. Chemical buffers form the first line of defense against added hydrogen ions (acid load; most common) or against added hydroxyl ions (less commonly).
3. In blood: When hydrogen ions are added, they combine with bicarbonate and form carbonic acid.
4. In urine: Secreted hydrogen ions combine with ammonia to form ammonium. Secreted hydrogen ions also combine with diphosphate to form monophospate.