[box type=”download”] Normal values Normal range of arterial blood pH and the importance of maintenance of this range Henderson-Hasselbach equation for bicarbonate and CO2 equilibrium The anion gap – components and calculation [/box]
The pH of arterial blood is 7.35–7.45 ([H+] = 45–35 nmol/L).
Metabolism produces ∼60 mmol H+ per day, most of which is excreted through the lungs as CO2, formed by the reaction of H+ + HCO3 − = H2O+CO2.
The kidneys conserve and replace HCO3− lost in this way, and fine tune H+ excretion.
Physiological buffers maintain a low free [H+] and prevent large swings in pH.
Buffers are weak acids (HA) or bases (A−) that can donate or accept H+ ions.
The ratio between buffer pairs (e.g. carbonic acid, H2CO3, and bicarbonate, HCO3−) is determined by [H+] and the dissociation constant (K) for that buffer pair: K = ([H+][A−])/[HA], or pH = pK + log([A−]/[HA]) (the Henderson– Hasselbalch equation).
Thus, an increase in [A−] or a decrease in [HA] will increase pH (more alkaline), and a decrease in pH will decrease the ratio [A−]/[HA].
Buffers work best when the pH is close to their pK value, the pH at which the ratio [A−]/[HA] is unity.
Bicarbonate and carbonic acid (formed by the combination of CO2 with water, greatly potentiated by carbonic anhydrase, CA are the most important buffer pair in the body, although haemoglobin provides ∼20% of buffering in the blood; phosphate and proteins provide intracellular buffering. Buffers in urine (ammonia and phosphate) allow the excretion of large quantities of H+.
Although the HCO3− system has a pK value of 6.1, and is theoretically a poor buffer at pH 7.4, it is physiologically effective because CO2 (and therefore H2CO3) and HCO3− are precisely controlled by the lungs and kidney, respectively.
These fix the HCO3−/ H2CO3 ratio and therefore the pH, and the latter determines the ratio of all other buffer pairs.
The line BAC (in davenport diagram) is the buffer line for whole blood; changes in PCO2 alter HCO3− and pH along this line. Point A denotes normal conditions (pH 7.4, [HCO3−] = 24 mM, PCO2= 5.3 kPa).
Anion gap
The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum.
Because potassium concentrations are very low, they usually have little effect on the calculated gap. Therefore, omission of potassium has become widely accepted.
Anion Gap = Na+ – (Cl- + HCO3-)
The normal value for the serum anion gap is 4 to 12mmol/L (if measured by ion selective electrode; 8 to 16 if measured by older technique of flame photometry.
A urine anion gap of more than 20 mEq/L is seen in metabolic acidosis when the kidneys are unable to excrete ammonia (such as in renal tubular acidosis). If the urine anion gap is zero or negative but the serum AG is positive, the source is most likely gastrointestinal (diarrhea or vomiting).
Renal regulation of acid – base balance
[box type=”download”] Urinary acidification (bicarbonate reabsorption + acid formation + handling of ammonia) The kidneys as net renal excretors of acid Factors influencing renal secretion and excretion of hydrogen ions[/box]
Proximal renal tubule
Bicarbonate is freely filtered, and so filtrate [HCO3−] is ∼24 mmol/L (as in plasma) and ∼80% is reabsorbed in the proximal tubule.
HCO3− is not transported directly.
Filtered HCO3− associates with H+ secreted by epithelial Na+–H+ antiporters to form H2CO3, which rapidly dissociates to CO2 and H2O in the presence of carbonic anhydrase.
CO2 and H2O diffuse into the tubular cells, where they recombine into H2CO3, which dissociates to H+ and HCO3−.
HCO3− is transported into the interstitium largely by Na+–HCO3− symporters.
For each H+ secreted into the lumen, one HCO3− and one Na+ enter the plasma.
H+ is recycled, so that there is little net H+ secretion at this stage.
A further 10–15% of HCO3− is similarly reabsorbed in the thick ascending loop of Henle.
In total, about 4000–5000 mmol of HCO3− is reabsorbed per day.
Ammonia
is produced in tubular cells by the metabolism of glutamine, which leads to the generation of HCO3− and glucose or CO2.
NH3 diffuses into the tubular fluid, or as NH4+ is transported by the Na+–H+ antiporter.
In the tubular fluid, NH3 gains H+ to form NH4+, which cannot diffuse through membranes.
About 50% of NH4+ secreted by the proximal tubule is reabsorbed in the thick ascending loop of Henle, where it substitutes for K+ in the Na+–K+–2Cl− symporter, and passes into the medullary interstitium.
Here, NH4+ dissociates into NH3 and H+, and NH3 re-enters the collecting duct by diffusion.
The secretion of H+ in the collecting duct leads to conversion back to NH4+, which is trapped in the lumen and excreted.
Distal renal tubule
The secretion of H+ in the distal tubule promotes the reabsorption of any remaining HCO3−.
The combination of H+ with NH3 and phosphate prevents H+ recycling and allows acid excretion.
In the early distal nephron, H+ secretion is predominantly by Na+–H+ exchange, but more distally secretion is via H+ ATPase and H+–K+ ATPase in intercalated cells, which contain plentiful carbonic anhydrase.
As secreted H+ is derived from CO2, HCO3− is formed and returns to the blood.
In summary, in the proximal nephron, H+ secretion promotes HCO3− reabsorption.
In the distal nephron, secretion leads to the combination of H+ with urinary buffers (phosphate, NH3), and thus the generation of HCO3− and acid excretion.
As a result of this, tubular fluid becomes more acid as it moves through the nephron.
H+ secretion is proportional to intracellular [H+], which is itself related to extracellular pH.
A fall in blood pH will therefore stimulate renal H+ secretion.
Metabolic disturbance
[box type=”download”] The typical ABG features of metabolic + respiratory alkalosis and acidosis An understanding of the primary systemic compensations which occur in each type[/box]
Acid–base regulation and compensation
Respiratory acidosis and alkalosis refer to alterations in pH caused by changes in PCO2 (i.e. ventilation).
Metabolic acidosis and alkalosis refer to changes not related to PCO2 (i.e. increased acid production, diet, renal disease, diabetic ketoacidosis).
Thus, hypoventilation increases PCO2 and causes respiratory acidosis, which may be compensated by increased renal excretion of H+ and reabsorption of HCO3−.
The [HCO3−]/PCO2 ratio is thus restored, and the pH returns towards normal.
Similarly, metabolic acidosis may be compensated by increased ventilation and reduced PCO2 (respiratory compensation), initiated by the detection of acid pH by the chemoreceptors.
Renal mechanisms are slow because their capacity for handling H+ and HCO3− is smaller than that of the lungs for handling CO2.