Normal human physiological pH is 7.35 to 7.45. A decrease in pH below this range is acidosis, an increase in this range is alkalosis. Hyperchloremic acidosis is a metabolic disease state disease state where acidosis (pH less than 7.35) with an ionic chloride increase develops. Understanding the physiological pH buffering process is important. The primary pH buffer system in the human body is the HCO3 (Bicarbonate)/CO2 (carbon dioxide) chemical equilibrium system. Where:
HCO3 functions as an alkalotic substance. CO2 functions as an acidic substance. Therefore, increases in HCO3 or decreases in CO2 will make blood more alkalotic. The opposite is also true where decreases in HCO3 or an increase in CO2 will make blood more acidic. CO2 levels are physiologically regulated by the pulmonary system through respiration, whereas the HCO3 levels are regulated through the renal system with reabsorption rates. Therefore, hyperchloremic metabolic acidosis is a decrease in HCO3 levels in the blood.
Anytime a metabolic acidosis is suspected, it is extremely useful to calculate the anion gap. This is defined as:
Where Na is plasma sodium concentration, HCO3 is plasma bicarbonate concentration, and Cl is plasma chloride concentration.
The anion gap is a calculation to determine the quantity of ionically active components within the blood that are not routinely measured. Since there are always components not directly measured, we expect this value to not equal 0. The primary unmeasured physiologically is albumen. A normal serum anion gap is measured to be 8 to 16 mEq/L. An increase in the anion gap is associated with renal failure, ketoacidosis, lactic acidosis, and ingestion of toxins, whereas a lowered bicarbonate concentration characterizes a normal anion gap acidosis. The human body is very good at remaining balanced ionically under most scenarios. As a result, with loss of the negatively charged ion bicarbonate, negatively charged chloride ion is displaced to the extracellular space. This leads to a narrow anion gap, electrically neutral state without correcting the pathology that induced the acidosis. Likewise, increased Cl (chloride) may displace bicarbonate intracellularly. Determining exact etiology of a narrow anion gap hyperchloremic acidosis requires another test, the urine anion gap. Urine anion gap is calculated:
Where Na is urine sodium, K is urine potassium, and Cl is urine chloride. The urine anion gap provides an estimate of urinary ammonium (NH4) excretion. The normal renal response to metabolic acidosis is to increase acidic NH4 excretion renally. Therefore, a positive urine anion gap between 20 and 90 mEq/L is indicative of low or normal NH4 excretion, such as is seen in distal renal tubular acidosis. A negative urine anion gap between -20 and -50 mEq/L is indicative of increased NH4 excretion. This occurs in patients with metabolic acidosis generated by profuse watery diarrhea. A urine anion gap approaching 0 is indeterminate.
Prevalence of hyperchloremic acidosis is unknown. The exact frequency and distribution of disease are dependent upon the etiology. Likewise, the morbidity and mortality rates are dependent on the etiology of the disease.
Hyperchloremic metabolic acidosis is a pathological state that results from bicarbonate loss, rather than acid production or retention. Bicarbonate loss leading to hyperchloremic metabolic acidosis occurs in a variety of ways: gastrointestinal (GI) causes, renal causes, and exogenous causes. GI loss of bicarbonate occurs through severe diarrhea, pancreatic fistula, nasojejunal tube suctioning from the duodenum, and chronic laxative use. Renal sources of hyperchloremic acidosis include proximal renal tubular acidosis, distal renal tubular acidosis, and long-term use of carbonic anhydrase inhibitors. Exogenous causes include ingestion of acids such as ammonium chloride and hydrochloric acid and volume resuscitation with 0.9% normal saline.
Normally, there is a degree of bicarbonate secreted into the intestinal lumen to allow for neutralization of the acidic environment of food from gastric emptying. Over the distance of the small intestines, this bicarbonate is reabsorbed as bile. However, in pathologies with profuse watery diarrhea, bicarbonate within the intestines is lost through the stool due to increased motility of the gut. This leads to further secretion of bicarbonate from the pancreas and intestinal mucosa leading to a net acidification of the blood from bicarbonate loss. Likewise, pancreatic fistula leads to excessive bicarbonate secretion from the pancreas into the intestines. This excess bicarbonate is ultimately lost in stools. Nasojejunal suctioning removes bicarbonate from the duodenal or jejunal space via direct suctioning of the luminal contents.The overarching theme with these pathologies is loss of bicarbonate from the gastrointestinal spaces which leads to an acidotic state in the blood via unopposed hydrogen in the buffering system as above.
Distal renal tubular acidosis (type 1) is a failure of the distal nephron to secrete hydrogen appropriately into urine. This results in alkalotic urine and acidosis of the blood. Failure to secrete hydrogen directly correlates with the NH4 levels in urine and is able to be deduced via a positive urine anion gap as above. Proximal renal tubular acidosis (type 2) is a pathology where bicarbonate is failed to be reabsorbed appropriately. This leads to loss of bicarbonate into the urine. The net result is acidosis of blood and alkalotic urine. Both types of renal tubular acidosis are associated with hypokalemia. Carbonic anhydrase inhibitors such as acetazolamide create a medically induced type 2 proximal renal tubular acidosis scenario by inhibiting bicarbonate reabsorption in the proximal nephron.
Many of the exogenous causes of hyperchloremic acidosis as logical evaluations. When substances such as ammonium chloride and hydrochloric acid are supplemented into the body, they react with bicarbonate in an attempt to buffer the pH. However, this will deplete bicarbonate stores leading to an acidotic state. Large volume resuscitation with 0.9% normal saline leads to an overload of chloride ions into the blood. As stated previously, chloride and bicarbonate work together to maintain an ionic balance of the cellular space. Hyperchlorhydria forces bicarbonate to move intracellularly to maintain ionic equilibrium, thus reducing the available bicarbonate for the pH buffering system leading to net acidosis.
Patients with hyperchloremic acidosis have no effects due to the hyperchloremia necessarily. However, the acidosis can have many poor health effects. A headache, lack of energy, nausea, and vomiting are common complaints, however as acidosis worsens stupor, coma, myocardial instability or arrest may occur. It is expected to see an increase in respiratory rate as the body attempts to decrease CO2 in compensation, however, in long-standing disease this may lead to muscle fatigue and respiratory failure.
A physical exam may show altered mental status, tachycardia, tachypnea, accessory muscle use with respiration, neurological deficits, muscular weakness, cardiac arrhythmias, cardiac murmurs, respiratory wheezing, rales, or rhonchi.
As with any illness, a detailed history and physical exam is the most important initial step in evaluation. Hyperchloremic acidosis due to gastrointestinal bicarbonate loss or medication usage is apparent easily. A complete blood count (CBC) to evaluate for an infectious cause with elevated white blood count and fluid body status with hemoglobin and hematocrit values is useful. A complete metabolic panel is important with attention to sodium, potassium, and chloride levels as these can be used to calculate the anion gap value. Arterial blood gas measurement is needed to determine pH status and to identify that the acidosis is metabolic in origin. Urinary anion gap is an essential measurement in hyperchloremic acidosis to establish the urine ammonium excretion status as discussed above. Distal renal tubular acidosis will have urinary pH greater than 5.3 and a positive urinary anion gap. In proximal renal tubular acidosis, urinary pH is usually less than 5.3, and urinary anion gap is variable.
Patients with hyperchloremic acidosis have no effects due to the hyperchloremia necessarily. However, the acidosis can have many poor health effects. A headache, lack of energy, nausea, and vomiting are common complaints. However as acidosis worsens stupor, coma, myocardial instability or arrest may occur. It is expected to see an increase in respiratory rate as the body attempts to decrease CO2 in compensation, however, in long-standing disease this may lead to muscle fatigue and respiratory failure.
In every case of hyperchloremic acidosis, the primary treatment is aimed at identifying and treating the inciting event of pathology. If respiratory fatigue and failure occur, these patients will need to be intubated and placed on mechanical ventilation. Hyperventilation of the patient on ventilator control can help reduce the acid load. In gastrointestinal causes, it is essential to administer intravenous (IV) saline to maintain fluid load as patients will easily dehydrate from diarrhea or suctioning of the intestines. Additionally, electrolytes need to be monitored and replenished as applicable. Of specific importance is the potassium level. The acidosis is moderated by supplementing bicarbonate into the saline fluids until the underlying pathology is repaired. In renal tubular acidosis, large quantities of bicarbonate administration may be necessary. If fluid overload is a concern, diuretics with supplemental potassium may be administered for some effect. If the acidosis is resistant to therapy, it may be necessary to utilize dialysis therapy.
As always, a variety of medications are known to induce hyperchloremic acidosis and should be avoided or used with caution. Gastrointestinal bicarbonate loss is known to occur with calcium chloride, magnesium sulfate, and cholestyramine use. Proximal renal tubular acidosis is associated with streptozotocin, lead, mercury, arginine, valproic acid, gentamicin, ifosfamide, and outdated tetracycline usage. Distal renal tubular acidosis is associated with amphotericin B, toluene, nonsteroidal anti-inflammatory drugs, and lithium use.
Differential diagnoses include the following: