Most cases of metabolic acid/base disturbances are associated with fluid and/or electrolyte imbalances and are more complicated to interpret and to understand the underlying pathophysiology than are acid/base disturbances of respiratory origin. On the following pages are exemplary results for different metabolic acid/base disturbances and an explanation of the pathophysiology involved.
A simple model of metabolic acidosis illustrating the characteristic feature of decreased HCO3 - can be conceived by imagining the consequences of injecting a significant amount of concentrated HC1 into an experimental subject. The injected acid would be immediately buffered by HCO3 - which would be converted into an equivalent amount of CO2 . The increased CO2 would be eliminated immediately by a brief increase in respiration so that an increase in PCO2 would not be detected. The essentially instanteous respiratory elimination of the increased dissolved CO2 is due to the rapid equilibration of the neutral, small molecule between blood and CSF. The consequent decrease in CSF pH is sensed by central chemoreceptors to stimulate respiration. Once the excess dissolved CO2 is eliminated and the PCO2 is normal, CSF pH and respiration rate return to normal. The net immediate effect is decreased pH with decreased HCO3 - and normal PCO2 .
The rapid elimination of excess dissolved CO2 does not represent respiratory compensation. Respiratory compensation develops as CSF HCO3 - equilibrates with blood HCO3 -. The half-time for this process is about 2 hours. As CSF HCO3 - decreases, so does CSF pH with consequent stimulation of respiration and decreased PCO2 . The decrease in PCO2 represents respiratory compensation to metabolic acidosis. Almost all cases of metabolic acid/base disturbances develop over a time period of several hours to days so that respiratory compensation is always complete to the extent possible.
Though Blood gas results completely reveal the nature of metabolic acid/base disturbances, the 6-7 panel chemistry results provide more revealing information.
E. Renal Tubular Acidosis:
RTA is a rare condition caused by a genetic defect in H+ secretion, and consequently deficient HCO3 - reabsorption and formation. The condition represents a simple example of metabolic acidosis not complicated by fluid and electrolyte disturbances. Since the condition is chronic, respiratory compensation is complete as possible. Chloride is increased to the same extent that HCO3 - is decreased and the anion gap is normal. Serum K+ is normal despite the K+/H+ shift because of deficient H+ counter secretion and consequent increased renal K+ countersecretion associated with normal aldosterone-stimulated Na+ reabsorption. Potassium deficiency and hypokalemia occurs if potassium intake is not sufficient to counteract the increased renal potassium loss.
F. Metabolic Acidosis from Diarrhea:
Unabsorbed GI secretions represent the potential loss of up to 6 liters of fluid per day. The fluid is electrolyte poor, with respect to serum, except for HCO3 - which is lost in greater amounts than is acid. Persistent diarrhea causes serious dehydration and acidosis. The kidneys release renin in response to the hypovolemia and the increased formation of angiotensin-II causes decreased renal blood flow and increased adrenal cortical elaboration of aldosterone. The consequent increased distal tubule Na+ reabsorption causes increased H+ and K+ secretion, with relatively more H+ than K+ secretion because of the acidosis. Despite the intracellular H+/K+ shift, the serum potassium concentration is normal because of the absolute increase in renal K+ secretion. The loss of Na+ poor fluid and increased renal Na+ reab-sorption results in hypernatremia and hyperosmolality causing increased pituitary elaboration of ADH. Increased renal water reabsorption cannot improve the hypovolemia without intestinal absorption of ingested water so that hypernatremia and hyperosmolality persist. The decreased GFR, from decreased renal blood flow, causes corresponding increases in serum urea and creatinine concentrations. Serum urea is additionally increased because of increased renal water reabsorption so that the serum urea/creatinine ratio is increased. Total GI secretions are not so hypoosmolar as gastric fluid so there is less transfer of intracellular fluid in diarrhea than in vomiting and the quantity of lost fluid is greater in diarrhea.
G. Metabolic Alkalosis from Vomiting:
Gastric fluid contains a high content of acid and potassium and the fluid volume is substantial. Persistent vomiting results in alkalosis, hypokalemia and dehydration. The vomiting does not permit replacement of the lost fluid and electrolytes. The kidneys release renin in response to the hypovolemia and the increased formation of angiotensin-II causes decreased renal blood flow and increased aldosterone-stimulated renal Na+ reabsorption. The increased Na+ reabsorption is limited by the hypokalemia and alkalemia, but that which does occur is associated with H+ and K+ secretion further worsening the alkalemia and hypokalemia. The loss of the hypoosmolar, sodium poor gastric fluid, along with increased renal Na+ reabsorption, results in hypernatremia, but not markedly so because of transfer of intracellular fluid. The hyperosmolality stimulates pituitary release of ADH and maximum renal water reabsorption. Increased water reabsorption, without water ingestion, does not improve the hypovolemia and hypernatremia, but limits renal fluid loss as does decreased GFR from decreased renal blood flow. Serum concentrations of urea and creatinine are increased in proportion to the decreased GFR and urea is additionally increased because of increased water reabsorption so that the serum urea/creatinine ratio is increased.
H. Chronic Renal Failure:
The number of functioning nephrons diminishes as renal disease progresses. Glomerular filtration rate is directly proportional to the number of functioning nephrons. The concentration of substances in serum which are excreted solely by glomerular filtration, such as creatinine and urea, increases in direct proportion to decreases in GFR. In the example shown, the fraction of functioning nephrons is reduced to about 15 - 20% of normal and the serum urea and creatinine concentrations are correspondingly increased by a factor of 5 - 7. (The result for urea in the example is greater than 100 mg/dl.) The residual nephrons are able to maintain fluid and electrolyte balance until only a few percentage of functioning nephrons remain and the terminal, end stage of the disease is eminent. Individual nephrons have the capacity to excrete 3 - 5 times the amount of acid normally required so that acidosis is not noticeable until the fraction of functioning nephrons is reduced to about 20 - 30% of normal. In this example, the disease has progressed beyond this stage and metabolic acidosis has developed due to the accumulation of organic acids, phosphate, sulfate and urate. These substances are unmeasured anions and their accumulation accounts for the increased anion gap in the metabolic acidosis of renal disease. The anion gap in the example is:
A- = 140 mEq/L - (100 + 15) mEq/L = 25mEq/L