endocrine and metabolic disorders
Acid Base Regulation
Acid Base Balance
Acid-base balance is maintained by Chemical buffering Pulmonary activity Renal activity Chemical buffers are solutions that resist changes in pH. Intracellular and extracellular buffers provide an immediate response to acid-base disturbances. Bone also plays an important buffering role, especially of acid loads. A buffer is made up of a weak acid and its conjugate base. The conjugate base can accept H+and the weak acid can relinquish it, thereby minimizing changes in free H+concentration. A buffer system works best to minimize changes in pH near its equilibrium constant (pKa); so, although there are potentially many buffer pairs in the body, only some are physiologically relevant. The relationship between the pH of a buffer system and the concentration of its components is described by the Henderson-Hasselbalch equation: where pKa is the dissociation constant of the weak acid Themost important extracellular bufferis the HCO3−/CO2system, described by the equation: An increase in H+drives the equation to the right and generates CO2. This important buffer system is highly regulated; CO2concentrations can be finely controlled by alveolar ventilation, and H+and HCO3−concentrations can be finely regulated by renal excretion. The relationship between pH, HCO3−, and CO2in the system as described by the Henderson-Hasselbalch equation is thus: Or similarly, by the Kassirer-Bleich equation, derived from the Henderson-Hasselbalch equation: Note: to convert arterial pH to [H+] use: or Both equations illustrate that acid-base balance depends on theratioof carbon dioxide partial pressure (Pco2) and HCO3−, not on the absolute value of either one alone. With these formulas, any 2 variables can be used to calculate the third. Other important chemical buffersinclude intracellular organic and inorganic phosphates and proteins, including hemoglobin in red blood cells. Less important are extracellular phosphate and plasma proteins. ). Long-standing acidemia therefore contributes to bone demineralization and Osteoporosis . CO2concentration is finely regulated by changes in tidal volume and respiratory rate (minute ventilation). A decrease in pH is sensed by arterial chemoreceptors and leads to increases in tidal volume or respiratory rate; CO2is exhaled and blood pH increases. In contrast to chemical buffering, which is immediate, pulmonary regulation occurs over minutes to hours. It is about 50 to 75% effective and does not completely normalize pH. The kidneys control pH by adjusting the amount of HCO3−that is excreted or reabsorbed. Reabsorption of HCO3−is equivalent to excreting free H+. Changes in renal acid-base handling occur hours to days after changes in acid-base status. All of the HCO3−in serum is filtered as it passes through the glomerulus. HCO3−reabsorption occurs mostly in the proximal tubule and, to a lesser degree, in the collecting tubule. The H2O within the distal tubular cell dissociates into H+and hydroxide (OH−); in the presence of carbonic anhydrase, the OH−combines with CO2to form HCO3−, which is transported back into the peritubular capillary, while the H+is secreted into the tubular lumen and joins with freely filtered HCO3−to form CO2and H2O, which are also reabsorbed. Thus, the distally reabsorbed HCO3−ions are newly generated and not the same as those that were filtered. Decreases in effective circulating volume (such as occur with diuretic therapy) increase HCO3−reabsorption, while increases inparathyroid hormonein response to an acid load decrease HCO3−reabsorption. Also, increased Pco2leads to increased HCO3−reabsorption, while chloride ion (Cl−) depletion (typically due to volume depletion) leads to increased sodium ion (Na+) reabsorption and HCO3−generation by the proximal tubule. secretion and hence Metabolic Alkalosis . 