There are multiple reasons why disorders of blood chemistry may develop, including respiratory or renal disease, obesity, and medication. Resulting imbalances include acidosis [pH 7.45], and high or low levels of key electrolyte ions, including sodium, potassium, calcium, magnesium, chloride, hydrogen phosphate, and hydrogen carbonate [bicarbonate]. They may be acute or chronic, may occur with varying degrees of severity, and may not be sufficiently counteracted by the body's regulatory/compensatory mechanisms.
Electrolyte balance is normally regulated by the hypothalamus, kidneys, and various hormones, including antidiuretic hormone [ADH], aldosterone [a mineralocorticoid hormone], and parathyroid hormone [PTH]. Acid-base balance is linked to fluid and electrolyte balance, and is normally controlled and maintained by immediate buffer systems via the kidneys and the pulmonary system.[1] Respiratory acidosis and alkalosis are accompanied by compensatory renal bicarbonate retention and loss, respectively; metabolic acidosis and alkalosis are accompanied by compensatory hyperventilation and hypoventilation, respectively. Mixed metabolic disorders can occur [e.g., diabetic ketoacidosis complicated by vomiting], and evaluation depends on clinical history and examination, assessment of anion gap, serum electrolytes, and arterial blood gases. These disorders can be effectively evaluated by a stepwise pathophysiologic approach.[1][2]
Evaluation of respiratory acidosis
Respiratory acidosis occurs when arterial partial pressure levels of carbon dioxide [PCO₂] increase above the normal range of 35 to 45 mmHg, due to inefficient clearance of CO₂. This leads to an accumulation of hydrogen ions, causing the arterial pH to fall below 7.35. It may be acute or chronic, and failure to recognize and treat the underlying cause can lead to respiratory failure and death. Causes of respiratory acidosis include COPD, multilobar pneumonia, foreign body aspiration, drug use [such as sedatives, anesthetics, alcohol, narcotics], and oxygen therapy in patients with COPD.
Chronic respiratory acidosis is commonly caused by obesity and COPD.
Clinical features of respiratory acidosis include respiratory depression [hypoventilation], obtundation, hemodynamic instability, and respiratory muscle fatigue [accessory muscle use, dyspnea, tachypnea].
Evaluation of respiratory alkalosis
Respiratory alkalosis is an acid-base disorder characterized by a primary reduction in the arterial partial pressure of CO₂ below the normal range of 35 to 45 mmHg, leading to an increase in pH above 7.45 and a subsequent decrease in bicarbonate from a normal value of 24 mEq/L. The decrease in PCO₂ typically occurs as a result of alveolar hyperventilation with an excess of CO₂ excretion compared to production.[3] The etiologies of respiratory alkalosis are multiple and include pulmonary embolism, sepsis and systemic inflammatory response syndrome [SIRS], acute respiratory distress syndrome [ARDS], pneumonia, and hyperventilation syndrome.[3] Respiratory alkalosis can be acute or chronic in nature.
Evaluation of metabolic acidosis
Metabolic acidosis is indicated by an arterial pH of less than 7.35, a decrease in the plasma bicarbonate level, and/or a marked increase in the anion gap [calculated by subtracting the sum of major measured anions, chloride and bicarbonate, from the major measured cation, sodium]. Where the anion gap is normal [6-12 mEq/L], gastrointestinal or renal causes are common.[4] This is also referred to as hyperchloremic or non-anion gap metabolic acidosis. Where the anion gap is increased, causes include diabetic ketoacidosis, alcoholic ketoacidosis, lactic acidosis, kidney disease, or ingestion of methanol, ethanol, ethylene glycol, propylene glycol, 5-oxoproline [e.g., in patients with chronic ingestion of acetaminophen], or salicylic acid. With simple metabolic acidosis, the normal adaptive respiratory response will decrease the arterial PCO₂ 1.0 to 1.5 times the decrease in serum hydrogen carbonate [bicarbonate].[5]Acute metabolic acidosis is associated with increased morbidity and mortality because of its depressive effects on cardiovascular function, increased risk of cardiac arrhythmias, stimulation of inflammation, and suppression of the immune response.[6]
Evaluation of metabolic alkalosis
Metabolic alkalosis is an elevated arterial pH of above 7.45, and is the consequence of disorders that cause either a loss of hydrogen ions from the body or an increase in plasma bicarbonate from a normal value of 24 mEq/L. Causes include gastric secretion loss [e.g., vomiting] and mineralocorticoid excess. Patients may present with tingling, muscle cramps, weakness, cardiac arrhythmias, and/or seizures.[7][8] Some symptoms may be due to a decrease in circulating calcium, which occurs when the pH is high. Patients may develop serious or fatal arrhythmias and/or seizures without preceding symptoms. Compensatory metabolic alkalosis may be an incidental finding in patients with chronic respiratory acidosis.
Evaluation of hyponatremia
Defined as a serum sodium 7.3 and hydrogen carbonate [bicarbonate] >15 mEq/L].[22] It is most common in older patients with type 2 diabetes. Contributes to less than 1% of all diabetes-related admissions. However, mortality is high: at approximately 15%.[23]
Infection is the major precipitating factor, occurring in 30% to 60% of patients. Urinary tract infections and pneumonia are the most common infections reported.[22][24]
Acute cognitive impairment [lethargy, disorientation, stupor] is common and correlates best with effective serum osmolality. Coma is rare and, if seen, is usually associated with a serum osmolality >340 mOsm/kg [>340 mmol/kg].[23] Treatment includes correction of fluid deficit and electrolyte abnormalities and intravenous insulin.
Renal tubular acidosis
The term renal tubular acidosis [RTA] refers to a group of renal disorders in which there are defects in the reabsorption of bicarbonate or the excretion of hydrogen ions, or both. The acid retention or bicarbonate loss results in the development of hyperchloraemic metabolic acidosis.
Therefore the RTA syndromes are characterized by a relatively normal GFR and a metabolic acidosis accompanied by hyperchloremia and a normal anion gap.[25] Adult patients with RTA are often asymptomatic but may present with muscular weakness related to associated hypokalaemia, nephrocalcinosis, or recurrent renal stones.
Proximal and classic distal RTA are characterized by hypokalemia.[26][25] Hyperkalemia in distal RTA indicates that aldosterone deficiency or resistance is the cause of the problem.[25] There is minimal or absent urine ammonium in hyperkalemic distal RTA. Serum sodium is usually normal. RTA is rarely symptomatic. Patients with severe acidemia can show hyperventilation or Kussmaul breathing due to respiratory compensation. The urine pH exceeds 5.5 in classic distal RTA, but is lower than 5.0 in patients with untreated proximal RTA. Alkali therapy is the mainstay of treatment in all forms of RTA.
Primary aldosteronism
Aldosterone’s primary function is to regulate sodium absorption and potassium excretion in the distal tubule. In primary aldosteronism [PA], aldosterone production exceeds the body's requirements and is relatively autonomous with regard to its normal chronic regulator, the renin-angiotensin II [AII] system.[27][28] This results in excessive sodium reabsorption via the distal nephron, leading to an increase in the volume of water taken up through the nephron contributing to the development of hypertension and suppression of renin-AII.
Urinary loss of potassium and hydrogen ions, exchanged for sodium at the distal nephron, may result in hypokalemia and metabolic alkalosis if severe and prolonged, however, most of patients are normokalemic.[27][28]
Primary aldosteronism is the most common specifically treatable and potentially curable form of hypertension, accounting for at least 5% of hypertensive patients. Approximately 30% have unilateral forms correctable by unilateral laparoscopic adrenalectomy, and 70% have bilateral forms in which hypertension responds well to aldosterone antagonist medication.[29]
Addison disease
Primary adrenal insufficiency, or Addison disease, is a disorder that affects the adrenal glands, causing decreased production of adrenocortical hormones [cortisol, aldosterone, and dehydroepiandrosterone]. This may be caused by a destructive process directly affecting the adrenal glands or a condition that interferes with hormone synthesis. Approximately 90% of the adrenal cortex needs to be destroyed to produce adrenal insufficiency. Addison disease may be either acute [adrenal crisis] or insidious. It presents with substantial fatigue and weakness associated with mucocutaneous hyperpigmentation, hypotension and/or postural hypotension, and salt craving. The finding of low sodium and high potassium serum levels is typical. If untreated, it is a potentially life-threatening condition. Adrenocorticotropic hormone stimulation test is performed to confirm or exclude the diagnosis of Addison disease.
All patients receive mineralocorticoid and glucocorticoid replacement for life, and are instructed to increase the dose of glucocorticoid during surgery and during any stressful or infectious conditions.
Syndrome of inappropriate antidiuretic hormone
Syndrome of inappropriate antidiuretic hormone [SIADH] is defined as euvolemic, hypotonic hyponatremia secondary to impaired free water excretion, usually from excessive antidiuretic hormone[ADH] secretion either from the pituitary or more commonly a nonpituitary source which may include medication or cancer [lung malignancy is the most common].
Antidiuretic hormone [ADH], also known as arginine vasopressin, facilitates free water absorption in the collecting tubule. Inappropriate secretion is characterized by hypotonic hyponatremia, concentrated urine, and a euvolemic state. It is primarily identified by abnormal serum sodium levels on laboratory testing, but patients may present with signs of cerebral edema, including nausea, vomiting, headache, mental status changes, increased somnolence, or coma, and appear euvolemic.