Metabolic compensation

Respiratory acidosis and alkalosis result from primary disturbances in the arterial carbon dioxide (C02) levels. Metabolic compensation of respiratory disturbances is a slow process, often requiring days for the serum HC03 to reach the steady state. 

Changes that follow the primary disorder and attempt to restore the blood pH to normal are referred to as compensatory changes. It should be stressed that compensation never normalizes the pH. Because all metabolic acid-base disorders are chronic and the normal respiratory system can quickly alter the PaC02, essentially all metabolic disorders are accompanied by some degree of respiratory compensation.3 Similarly, chronic respiratory acid-base disorders are typically accompanied by attempts at metabolic compensation.4,5 However, with acute respiratory acid-base disorders there is insufficient time for the metabolic pathways to compensate significantly.6 As such, acute respiratory derangements are essentially uncompensated. 

It is critical to differentiate acute and chronic respiratory acidosis, as the acute form is often a medical emergency that requires intubation and mechanical ventilation, whereas the chronic form is typically a stable condition. The blood gases in Case Study 2 came from a patient with advanced emphysema who is a "C02 retainer" due to ineffective ventilation. Because this patient s disease is chronic, the elevated PaC02 developed very slowly and allowed for metabolic compensation. 

Now consider a psychiatric patient who presents with a pH of 7.50, a PaC02 of 20 mm Hg (2.7 kFh), an HC03 of 16 mEq/L (mmol/L), a sodium concentration of 140 mEq/L (mmol/L), and a chloride level of 103 mEq/L (mmol/L). Because this person is alkalemic, the low PaC02 is the primary disturbance and represents respiratory alkalosis. If this disturbance is a chronic respiratory alkalosis with metabolic compensation, the expected AHC03 is 0.4 x APaC02 (in millimeters of mercury) or 0.4 x 20, which is 8 mEq/L (mmol/L). As such, the predicted HC03 concentration should be 24 mEq/L (mmol/L) [normal] - 8 mEq/L (mmol/L) [expected compensation] or 16 mEq/L (16 mmol/L). 

B15. Beutler, E., Carson, D., Dannawi, H., Forman, L., Kuhl, W., West, C., and Westwood, B., Metabolic compensation for profound erythrocyte adenylate kinase deficiency A hereditary enzyme defect without hemolytic anemia. J. Clin. Invest. 72,648-655 (1983). 

Patients with partial enzymatic deficiencies may present later in life with intermittent ketoacidosis, prostration and recurrent ataxia. The plasma concentrations of BCAA are elevated during these episodes but they maybe normal or near-normal during the periods when patients are metabolically compensated. 

McCue, K. F., Shepherd, L. V. T., Allen, P. V, Maccree, M. M., Rockhold, D. R., Corsini, D. L., Davies, H. V, Belknap, W. R. (2005). Metabolic compensation of steroidal glycoalkaloid biosynthesis in transgenic potato tubers using reverse genetics to confirm the in vivo enzyme function of a steroidal alkaloid galactosyltransferase. Plant science, 168, 267-273. 

There is a large and somewhat contentious literature dealing with the question of how fully the respiratory rates of ectotherms can be adjusted to offset g10 effects on metabolic reactions, a process known as temperature compensation of metabolism. Metabolic compensation... 

As with the metabolic acid-base disturbances, there are two cardinal respiratory acid-base disturbances respiratory acidosis and respiratory alkalosis. These disorders are generated by a primary alteration in carbon dioxide excretion, which changes the concentration of carbon dioxide, and therefore the carbonic acid concentration in body fluids. A primary reduction in PaC02 causes a rise in pH (respiratory alkalosis), and a primary increase in PaC02 causes a decrease in pH (respiratory acidosis). Unlike the metabolic disturbances, for which respiratory compensation is rapid, metabolic compensation for the respiratory disturbances is slow. Hence these disturbances can be further divided into acute disorders, with a duration of minutes to hours that is too short for metabolic compensation to have occurred, and chronic disorders, that have been present long enough for metabolic compensation to be complete. 

Metabolic compensation occurs when respiratory alkalosis persists for more than 6 to 12 hours. In response to the alkalemia, proximal tubular bicarbonate reabsorption is inhibited and the serum bicarbonate concentration falls. Renal compensation is usually complete within 1 to 2 days. The renal bicarbonaturia, as well as decreased NH4+ and titratable acid excretion, are direct effects of the reduced PaC02 and pH on renal reabsorption of chloride and bicarbonate. The... 

The decrease in ion levels and suppression of ATPase activities in snails and mus.sels exposed to subacute concentration on day 5 also indicated the inhibition of ionic exchange under mercury stress. But, as the stress is subacute, these animals made an effort to recover from the impact on further exposure thereby the degree of suppression of ATPase activities decreased on day 15 with a tittle rise in the levels of ions relative to day 5. The activation of detoxification mechanisms and metal elimination processes might have facilitated for such metabolic compensation. Interestingly, the ability of compensation improved in mussels on further exposure of them to 30 days as revealed by the attainment of normal levels of ions and ATPases in their hepatopancreas whereas the snails could not tolerate the prolonged impact of stress, hence the level of ions and ATPases in them exhibited a significant decrease. 

Meade et al. [24] reported the responses of heat and oxygen flux to varying levels of environmental oxygen for the Australian crayfish Che rax quadricarinatus. When crayfish were exposed to p y2 values less than approximately 5 kPa, both heat dissipation and oxygen uptake were depressed. However, the depression of heat dissipation was only transient, and it recovered to normoxic values within 4 h, which suggested some form of metabolic compensation. CR ratios at or below the critical Pq2 were not determined, so the quantitative contribution of anaerobic pathways to any compensation could not be estimated. These juvenile crayfish were incapable of surviving a 1-2 h anoxic treatment at 28"C. 

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