Renal Mechanisms

The kidneys maintain acid-base balance by excreting hydrogen ions (H⁺) and reabsorbing bicarbonate (HCO₃⁻):

- **H⁺ Excretion**: The kidneys secrete H⁺ into the urine, which combines with urinary buffers (e.g., phosphate) to form substances excreted in the urine.
- **HCO₃⁻ Reabsorption**: The kidneys reabsorb bicarbonate from the urine back into the blood, which helps neutralize acids.
- **Ammonium Production**: The kidneys produce ammonium (NH₄⁺) from amino acid metabolism, which acts as an additional mechanism for H⁺ excretion.

 

### Pathological Conditions

- **Acidosis**: An excess of acid in the body (pH < 7.35). It can be respiratory (due to CO₂ retention) or metabolic (due to HCO₃⁻ loss or H⁺ gain).
- **Alkalosis**: An excess of base in the body (pH > 7.45). It can be respiratory (due to CO₂ loss) or metabolic (due to HCO₃⁻ gain or H⁺ loss).

In summary, the body achieves acid-base balance through the combined efforts of buffer systems, the respiratory system, and the renal system, each playing a crucial role in maintaining a stable internal environment.

 

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Cell membranes and sub­cellular particle membranes consist of specific proteins which are amphoteric and are sensitive to small changes in the hydrogen ion concentration of their en­vironment.

Many extracellular proteins such as the plasma proteins and membrane proteins of the body's cells are very sensitive for their three dimensional structures to the extracellular pH.

It is possible that the tertiary and quaternary structure of the lipoprotein membranes, and hence the membrane characteristics, may be altered by the hydrogen ion concentration of the bathing fluid. Thus the normal metabolic activity of the cell and of the whole animal will be adversely affected by wide changes in hydrogen ion concentration.

Outside the acceptable range of pH, proteins are denatured (i.e. their 3-D structure is disrupted), causing enzymes and ion channels  to malfunction.

 

 

Chemical Buffering

Intracellular H+ buffering power and its dependency on intracellular pH. Intracellular hydrogen ion (H+) buffering power, conventionally defined as the amount of acid or base that would have to be introduced into the cell cytosol to decrease or increase ipH by one pH unit, is generally said to increase as intracellular pH (ipH) decreases. This implies that the cell has a lesser capability to resist acute acid or base perturbations at its steady state ipH than at any lower ipH. We re-examined this notion, reasoning that the logarithmic nature of the pH unit could limit the validity of the conventional expression of buffering power in imparting physiologic insight into the mechanisms of cellular H+ homeostasis. The mathematical derivation of the formula, aJNH4 +j/ajpH, conventionally used to estimate buffering power using the NH4CI technique, revealed that this parameter is, by design, inversely proportional to the exponential of ipH. This a priori dependence on pH dictates an increase in buffering power with decreasing ipH, and thereby interferes with the assessment of the physiologic capability of the intracellular milieu to buffer protons at different ipH levels. To circumvent this problem, buffering power was defined as the amount of hydrogen ions that would have to be added to or removed from the cell to effect a change in the concentration of H+ in the cell cytosol of I mM (a term heretofore referred to as the cell H+ buffering coefficient). The mathematical derivation of the formula used to calculate the cell H+ buffering coefficient, aJNH4 +j/MH+jj, does not suffer from an a priori dependence on ipH. U sing this approach we found that in rat thymocytes suspended in a HCOiC02 solution, the total cell buffering coefficient decreased as ipH was lowered from 7.3 to 6.6. The decrease in total cell buffering coefficient was associated with a decrease in the buffering power of buffers other than CO2/HC03 (that is, the intrinsic buffering coefficient), therefore unravelling a pattern of dependence on ipH that is the opposite of that portrayed by the conventional expression of the buffering power. The component of intracellular buffering contributed solely by the HCOiC02 system also decreased with decreasing ipH as expected in an open buffer system. We, thus, conclude that the intrinsic cell H+ buffering power, estimated from the use of the cell buffering coefficient, decreases as ipH is reduced from 7.3 to 6.6 whereas it increases when estimated by the conventional approach. The coefficient of cell H+ buffering, unlike the traditional buffering power, provides insight into the physiologic ipH dependency of the cell's capability to resist acute acid or base perturbations.

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The control of arterial CO2 tension (PaCO2) by the central nervous system (CNS) and respiratory system and the control of plasma bicarbonate by the kidneys stabilize the arterial pH by excretion or retention of acid or alkali.

The metabolic and respiratory components that regulate systemic pH are described by the Henderson-Hasselbalch equation:

 

Under most circumstances, CO2 production and excretion are matched, and the usual steady-state PaCO2 is maintained at 40 mmHg. Underexcretion of CO2 produces hypercapnia, and overexcretion causes hypocapnia. Nevertheless, production and excretion are again matched at a new steady-state PaCO2. Therefore, the PaCO2 is regulated primarily by neural respiratory factors and is not subject to regulation by the rate of CO2 production. Hypercapnia is usually the result of hypoventilation rather than of increased CO2 production. Increases or decreases in PaCO2 represent derangements of neural respiratory control or are due to compensatory changes in response to a primary alteration in the plasma [HCO3−].