ACID-BASE DISORDERS

Normal acid-base regulation in body revolves around the concentration of hydrogen (proton) ions in body fluids, denoted as pH-the negative algorithm of free H⁺ concentration.

Normal blood pH ranges between 7.35 and 7.45. H⁺ ions are continuously produced during various metabolic activities including dissociation of body acids (H⁺ donor), e.g. H₂CO₃ and neutralized by body bases (H⁺ acceptor), e.g. -OH, -HCO3, NH3, phosphates, etc.

Maintenance of normal blood pH depends on the rate of H⁺ ion production and their neutralization. Excess production or deficient neutralization of H⁺ ions lowers blood pH (acidosis), while reduced production or over­neutralization leads to increased pH (alkalosis).

Thus, actual blood pH depends on a ratio between its bases and acids, also depicted by Henderson-Hasselbalch equation, i.e.

pH= pK + log base/acid

*pK is a constant, derived from dissociation of acid-base pair. As H⁺ ions are produced and eliminated at a variable rate, continuous regulation of normal acid-base balance depends on:

• Immediate buffering mechanisms to prevent rapid changes in pH, and

• Subsequent compensatory mechanisms to correct the actual biochemical change.

A. Buffering mechanisms: Immediately after production, H⁺ ions are neutralized by certain body buffers, i.e. the substances that resist sudden pH changes by accepting or releasing extra H⁺ ions.

The principal buffer in extracellular compartment (ECF) is bicarbonate-carbonic acid system, denoted by following bi-directional equation:

(H⁺) + (HCO₃^-) #8800; H₂CO₃ #8800; H₂O + CO₂

The direction in which this equation runs, depends on the rate of H⁺ production and their concentration in ECF.

• Rightward movement of this equation leads to exces­sive clearance of H⁺ ions (alkalosis), while leftward movement leads to accumulation of H⁺ ions (acidosis)

• Excess production of H⁺ or depletion of HCO₃^- - due to any cause, leads to excess of H⁺ ions in body (metabolic acidosis)

• Excess accumulation of HCO₃^- or depletion of H⁺ due to any cause, leads to deficit of H⁺ ions in body (metabolic alkalosis)

• Retention of CO₂ due to any cause drives this equation towards left, leading to inadequate buffering of H⁺ ions (respiratory acidosis)

• Hyperventilation with CO₂ wash-out derives this equation to the right, leading to rapid clearance of H⁺ ions (respiratory alkalosis)

Other important, though less efficient, buffer systems in body include, e.g. hemoglobin, proteins, phosphates, ammonia-ammonium buffer, etc.

B. Compensatory mechanisms: Abovementioned buffering mechanisms prevent rapid fluctuations in blood pH but do not correct the actual acid-base imbalance. Further, this neutralization leads to excess HCO3^- utilization, disturbing normal CO₂#8725;HCO₃^- ratio and limiting further buffering capacity.

Actual correction of acid-base imbalance after initial buffering is a slow process, which aims to normalize pCO₂#8725;HCO₃^- ratio and eliminate excess H⁺ ions by:

• Pulmonary regulation, i.e. increased/decreased excretion

of CO₂, by changes in respiratory rate/depth;

• Renal regulation by:

- increased/decreased reabsorption of HCO₃^- in proximal tubules and ascending loop of Henle,

Fig. 7.4: Pathophysiology of simple acid-base disorders

- replacement of depleted HCO₃^- by production of new HCO₃^- in distal tubules and collecting ducts,

- actual H⁺ excretion/secretion in distal tubules and collecting ducts.

In general, metabolic acidosis or alkalosis is compen­sated by pulmonary mechanisms, i.e. via increased or decreased CO₂ excretion respectively, while respiratory acidosis or alkalosis is compensated by renal mechanisms, i.e. increased or decreased HCO₃ excretion, respectively. Thus, any acid-base imbalance is corrected by a two- step process:

a. changes due to initial buffering mechanism (primary parameter) during early stages, and

b. changes due to compensatory mechanism (secondary parameter) after some time.

As a thumb rule, in uncompensated pH disturbance, primary parameter is altered but secondary parameter is normal. On the other hand, in compensated state, primary as well as secondary parameter move in same direction. For example, in uncompensated metabolic acidosis, primary parameter (HCO₃) is reduced but pCO₂ is normal, while in compensated state, both HCO₃ and pCO₂ are reduced.

Figure 7.4 summarizes important buffering and compensatory mechanisms in various acid-base disturbances.

7.6.2