THE CO2/HCO3- BUFFER SYSTEM HCO3- is present at a high concentration ( 24 mM), quantitatively therefore it is the most important extracellular

buffer. The buffer system is under the dual regulation of the lungs and the kidneys

The reaction is:

CO2 + H2O
CA

H2CO3

H+ + HCO3-

The first step is relatively slow and requires catalysis by the Zn2+dependent enzyme carbonic anhydrase (CA).

THE CO2/HCO3- BUFFER SYSTEM - WHY IS IT SO GOOD? What happen when acid is added for example?

H+ + HCO3-

H2CO3

CO2 + H2O

If acid is continually added the [CO2], or PCO2, would rise and so the reaction would slow down. However, what would happen if the CO2 were removed? H+ + HCO3H2CO3 CO2 + H2O

LUNGS The PCO2 would not rise so such an extent and the reaction could proceed more extensively.

THE HENDERSON-HASSELBALCH EQUATION

CO2 + H2O

H2CO3

H+ + HCO3[HCO3-] + [H+] [CO2] + [H2O]

The equilibrium for this reaction can be written: K =

On re-arrangement:

[HCO3-] [HCO3-] pH = pK + log = pK + log [CO2] a. PCO2

The Henderson-Hasselbalch eq

At 37C:

pK = 6.1

a = 0.03 mmol.l-1.mm Hg-1

REABSORPTION OF FILTERED HCO3-

proximal tubule

85% of filtered HCO3- is reabsorbed in the proximal tubule. H+ are secreted into the tubule and react with filtered HCO3- catalysed by carbonic anhydrase The CO2 formed diffuses into the cell where it generates HCO3- and H+ via carbonic anhydrase.

Na+ HCO3- + H+

Na+

ATP

H2CO3 CA H2O + CO2

H+ + HCO3H2CO3 CA CO2 + H2O Cl-

The HCO3- leaves via the baso-lateral membrane and the H+ is re-cycled.

Thus net HCO3- is reabsorbed by the proximal tubule.

REABSORPTION OF FILTERED HCO3HCO3- reabsorption is Na+ independent.

distal tubule

H+ are secreted by the apical membrane, via a H+-ATPase

HCO3- + H+

Intercalated cell
ATP

Extracellular and intracellular carbonic anhydrase again are vital to ensure an adequate reaction speed. HCO3 leaves the baso-lateral membrane via a HCO3--Clcounter-transporter
-

H2CO3 CA H2O + CO2

H+ + HCO3H2CO3 CA CO2 + H2O Cl-

THE FORMATION OF NEW HCO3- - THE ROLE OF NH3 Formation of new HCO3- is necessary to replenish that lost in buffering non-volatile acids produced by metabolism. This is achieved by production of urinary buffers in the kidney. These remove secreted by buffer + H+ the distal tubule/collecting duct H-buffer The protonated buffer is not reabsorbed from the tubular fluid This is achieved mainly by the production of NH3 from glutamine H+
ATP Intercalated cell H+ + HCO3-

H2CO3 CA CO2 + H2O

Cl-

THE FORMATION OF NEW HCO3- - THE ROLE OF NH3

In the proximal tubule (PT):

Glutamine 2NH4+ + 2HCO3DT

H+

H+ H+

HCO3 cross baso-lateral membrane NH4+ enter the tubular fluid.

NH4+

In the thick ascending limb (TAL)

NH4+ is reabsorbed and equilibrates with NH3 in the interstitium.

PT

TAL

NH4+/ NH3 NH4+/ NH3

CD

In the collecting duct (CD):

NH3 diffuses into the CD lumen and combines with H+ secreted by the DT/CD. The NH4+ are then excreted in the urine
NH4+

THE RELATIONSHIP BETWEEN PLASMA pH, [HCO3-] and PCO2

The Davenport diagram expresses the relationship between these variables [HCO3-], mM 32 28 24 20 16 12 7.1 7.2 7.3 7.4 7.5 7.6 7.7 pH plasma buffer line 60 mm Hg 40 mm Hg

20 mm Hg

RESPIRATORY ACIDOSIS A retention of CO2 generally caused by respiratory problems, hypoventilation

[HCO3-], mM 60 mm Hg 32 28 24

40 mm Hg

20 mm Hg

Asthma

20
16

12
7.1 7.3 7.5 7.7 pH

PCO2 is raised, pH is reduced HCO3- is normal

COMPENSATED RESPIRATORY ACIDOSIS Compensation attempts to restore the pH towards normal

[HCO3-], mM 32

2
28 24

40 mm Hg

20 mm Hg

The kidney retains base, i.e. HCO3Although the PCO2 remains elevated the pH approaches a normal value PCO2 is raised, pH is normalised HCO3- is raised

1
60 mm Hg

20
16 12 7.1

7.3

7.5

7.7

pH

RESPIRATORY ALKALOSIS Excessive loss of CO2 generally caused by hyperventilation

[HCO3-], mM 60 mm Hg 32
28 40 mm Hg 20 mm Hg

24
20 16 12 7.1 7.3

7.5

7.7 pH

PCO2 is reduced, pH is raised HCO3- is normal

COMPENSATED RESPIRATORY ALKALOSIS

[HCO3-], mM 60 32 mm Hg 28 24

40 mm Hg

20 mm Hg

The kidney loses net base, i.e. HCO3Although the PCO2 remains reduced the pH approaches a normal value PCO2 is reduced, pH is normalised HCO3- is lowered

1 2

20
16 12 7.1 7.3

7.5

7.7

pH

RESPIRATORY ACID-BASE CHANGES using the Henderson-Hasselbalch equation [HCO3-] pH = pK + log a. PCO2

Respiratory acidosis e.g. hypoventilation [HCO3-] pH = pK + log a. PCO2

Respiratory alkalosis e.g. hyperventilation [HCO3-] pH = pK + log a. PCO2

Compensation retention of base

[HCO3-] pH = pK + log a. PCO2

loss of base [HCO3-] pH = pK + log a. PCO2

METABOLIC ACIDOSIS

Many different diseases and medical conditions lead to metabolic acidosis Diabetes Heart failure

[HCO3-], mM 60 mm Hg 32
28

40 mm Hg

20 mm Hg

24
20 16

Renal failure

Diarrhoea

12 7.1 7.3 7.5 7.7 pH

PCO2 is unchanged, pH is reduced HCO3- is reduced

COMPENSATED METABOLIC ACIDOSIS

[HCO3-], mM 60 mm Hg 32 28 24 20 16 12 7.1 7.3 7.5 7.7 pH 40 mm Hg

20 mm Hg

The lungs excrete more CO2 hyperventilation Although the HCO3remains reduced the pH approaches a normal value HCO3- is reduced, pH is normalised PCO2 is lowered

METABOLIC ALKALOSIS
[HCO3-], mM 60 mm Hg 32
28 40 mm Hg 20 mm Hg

24
20 16 12 7.1 7.3 7.5 7.7 pH

Example: net loss of H+; e.g. through vomiting

PCO2 is unchanged, pH is increased HCO3- is increased

COMPENSATED METABOLIC ALKALOSIS

[HCO3-], mM 60 mm Hg 32 28 24 20 16 12 7.1 7.3 7.5 7.7 pH 40 mm Hg

20 mm Hg

The lungs excrete less CO2 hypoventilation Although the HCO3remains increased the pH approaches a normal value HCO3- is raised, pH is normalised PCO2 is raised

METABOLIC ACID-BASE CHANGES using the Henderson-Hasselbalch equation [HCO3-] pH = pK + log a. PCO2

Metabolic acidosis e.g. diarrhoea [HCO3-] pH = pK + log a. PCO2

Metabolic alkalosis e.g. vomiting [HCO3-] pH = pK + log a. PCO2

Compensation hyperventilation
[HCO3-] pH = pK + log a. PCO2

hypoventilation [HCO3-] pH = pK + log a. PCO2