Metabolic Acid/Base Disturbances

Metabolic Acid/Base Disturbances

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

I. Diabetic Keto-Acidosis:

Circulating glucose accumulates in insulin deficiency because of impaired entrance into cells and/or increased gluconeogenesis. Characteristic features of diabetic ketoacidosis include metabolic acidosis with an increased anion gap because of the accumulation of ketoacids, hyperlipidemia, and dehydration from fluid and electrolyte loss as a consequence of osmotic diuresis.
Triglycerides in adipocytes are continuously hydrolyzed and resynthesized. Resynthesis of triglycerides requires α-glycerol phosphate, the only source of which, in adipocytes, is from glycolysis, since the cells lack glycerol kinase. Triglyceride resynthesis is thus impaired in adipocytes of poorly controlled diabetics and free fatty acids accumulate and are transported in the circulation bound to albumin to be used instead of glucose as an energy source. The fatty acids are metabolized by ß-oxidation with the formation of acetylCoA to be further oxidized by mitochondria. However, oxidative phosphorylation is diminished with insulin lack so that the liver metabolizes fatty acids by ß-oxidation more rapidly than mitochondria can utilize the formed acetyl-CoA. The accumulated acetyl-CoA condenses to acetoacetic acid (ß ketobutyric acid). Bicarbonate buffering of the keto acid is the origin of the metabolic acidosis. The anion gap is increased because of increased concentration of the unmeasured anionic ß keto acid. The condition develops over a time period of several hours to days so that respiratory compensation is generally complete. More rapid development may occur from a precipitating factor such as infection or trauma.
Hyperlipidemia occurs because fatty acid transport to the liver is more rapid than fatty acid oxidation. Triglycerides are synthesized from the excess fatty acids and are excreted by the liver in the form of very low density lipoproteins.
Serum glucose concentration is generally at least 500 mg/dl. Since the renal transport maximum for glucose reabsorption is about 160 mg/dl, a significant amount of osmotically active glucose accumulates in the tubule fluid causing osmotic diuresis. The rate of fluid loss is proportional to serum glucose concentration above the renal Tm and is about 350 ml/hour at a serum glucose concentration of 500 mg/dl. The increased urine flow rate reduces the hyperosmolality of the renal medulla so that concentrating ability is diminished and urine osmolality is only about twice that of serum (~ 300 mOsM), rather than the expected maximum of 3 - 4 times that of serum in hypovolemic conditions, with glucose as the major osmotically active component but with considerable loss of K⁺ and Na⁺. Even though pituitary elaboration of ADH is increased in response to increased serum osmolality, water reabsorption is minimal. Renin release in response to hypovolemia minimizes sodium loss by decreasing GFR and increasing aldosterone stimulated Na⁺ reabsorption. Considerable K⁺ is lost in the urine, considering the acidotic state, because of movement of potassium rich intracellular fluid into the extracellular compartment as serum osmolality increases. The net result of the renal fluid and electrolyte losses and the movement of intracellular fluid into the extracellular compartment is normal serum K⁺ concentration and slight to moderate hyponatremia. The extent of urine sodium loss and consequent hyponatremia depends on the glucose elevation. Decreased GFR causes increased serum urea and creatinine concentrations by a factor of 2 - 4 and the serum urea/creatinine ratio is only slightly increased because of ineffective ADH stimulated water reabsorption.

J. Lactic Acidosis:

Lactic acidosis most commonly results from shock with severely impaired circulation to visceral organs and to skeletal muscle. The consequent hypoxia results in increased glycolysis and production of lactic acid which is buffered by HCO₃^-. The condition develops over a time period of several hours so that respiratory compensation is complete. Decreased renal perfusion pressure results in renin release and the increased angiotensin-II causes further reduction of renal blood flow as well as increased aldosterone stimulated Na⁺ reabsorption. Counter secretion of H⁺ is relatively greater than that of K⁺ but the absolute increase in K⁺ secretion maintains normokalemia despite the intracellular K⁺/H⁺ shift. The potential to develop hypernatremia and hyperosmolality is counteracted by increased pituitary elaboration of ADH and increased renal water reabsorption. The decreased GFR from decreased renal blood flow causes increased serum urea and creatinine concentrations. Increased water reabsorption causes an additional increase in serum urea so that the serum urea/creatinine ratio is in-creased. The accumulation of lactate, an unmeasured anion, causes an increased anion gap.

The three metabolic acidoses with increased anion gap are easily differentiated. The distinguishing feature of diabetic ketoacidosis is a serum glucose concentration about 500 mg/dl, or greater, along with total CO₂ in the vicinity of 10 mEq/L and serum urea 2-4 fold elevated. The distinguishing features of chronic renal failure include serum urea concentration in the vicinity of 100 mg/dl or greater, total CO₂ in the vicinity of 15 mEq/L and normal glucose concentration. In lactic acidosis, the total CO₂ is about 10 mEq/L, urea is 2-4 fold elevated and glucose is normal.

Last Updated: March, 14, 2016