Last reviewed: 21 Aug 2021
Last updated: 07 Sep 2021

Introduction

Condition
Description

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).

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.

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]

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.

Defined as a serum sodium <135 mEq/L; severe hyponatremia is defined as a serum sodium <120 mEq/L. Hyponatremia is a common electrolyte disorder and is estimated to occur in 15% of all hospital inpatients.[9][10]Patients with hyponatremia have increased morbidity and mortality.[11] With few exceptions, when the serum sodium level is low, plasma osmolality is also low (hypotonic hyponatremia). While defined by the level of sodium, hypotonic hyponatremia is, in fact, a disorder of water balance. Common causes are administration of hypotonic fluids to patients and use of thiazide diuretics (more likely to affect older people).[12] Hyponatremia may also be a clue to the presence of serious underlying medical disorders. Patients who develop hyponatremia as a result of head injury, intracranial surgery, subarachnoid hemorrhage, stroke, or brain tumors may have cerebral salt-wasting syndrome or syndrome of inappropriate antidiuretic hormone (SIADH). A decrease in aldosterone production (e.g., Addison disease) causes increased sodium loss from the kidney and hyponatremia.

Hypernatremia is defined as a plasma sodium concentration of >145 mEq/L. Hypernatremia is a state of hyperosmolality, and is primarily a result of water deficit or sodium gain. Normally, persistently high sodium levels trigger antidiuretic hormone (ADH) release, stimulating thirst mechanisms so that hypernatremia rarely develops. Hospitalized patients often have impaired thirst mechanisms, restricted access to water, and an increased risk of water loss (e.g., due to vomiting or fever). They are also at risk for iatrogenic inadequate fluid replacement. Endocrine abnormalities such as diabetes insipidus and mineralocorticoid excess may also lead to hypernatremia. Examination should focus on volume status.

Hypokalemia is a serum potassium level <3.5 mEq/L. Clinical manifestations are typically seen only if the serum potassium level is <3.0 mEq/L, and include muscle weakness, ECG changes, cardiac arrhythmias, rhabdomyolysis, and renal abnormalities. Hypokalemia may result from decreased potassium intake, increased potassium entry into cells, increased potassium excretion (e.g., from the gastrointestinal tract, via urine or sweat), dialysis, or plasmapheresis. There are multiple causes of hypokalaemia, including vomiting, severe diarrhoea, laxative and bowel cleansing agent use in bulimia nervosa, chronic alcoholism, anorexia nervosa,[13] renal tubular acidosis,[14] primary aldosteronism, salt-wasting nephropathies,[15] and cystic fibrosis.[16] Some medications can cause hypokalemia, including diuretics, insulin treatment for diabetic ketoacidosis or nonketotic hyperglycemia, beta-adrenergic agonists such as albuterol or terbutaline, theophylline, chloroquine, laxative abuse or bowel-cleansing agent use, and administration of vitamin B12 or folic acid in megaloblastic anemia.[14]

Significant hyperkalemia is defined as a serum potassium value >6.0 mEq/L. Moderate hyperkalemia is defined as serum potassium values in the 5.0 to 6.0 mEq/L range. Hyperkalemia can be life-threatening and may cause cardiac arrhythmias (ventricular fibrillation) by affecting the cardiac action potential. Hyperkalemia is often multifactorial in etiology. It may result from effective depletion of the circulating volume by heart failure combined with ACE inhibitors, or from increased dietary potassium intake combined with chronic renal failure. It is essential to take a thorough history of comorbidities and medications that might increase cellular potassium release or reduce urinary excretion. Reduced potassium excretion occurs in renal failure, volume depletion, and hypoaldosteronism.[17] Dietary factors (e.g., excess consumption of foods high in potassium) or medications may quickly lead to hyperkalemia in patients with comorbidities.

Hypocalcemia is a state of electrolyte imbalance in which the circulating serum calcium level is low. Hypocalcemia arises mainly from either insufficient entry of calcium into the circulation or an increased loss of calcium from the circulation. There are multiple causes, including iatrogenic postsurgical hypoparathyroidism (usually transient), vitamin D deficiency, hypomagnesemia, hyperventilation, hypoparathyroidism, pseudohypoparathyroidism, hyperphosphatemia, hungry bone syndrome (rapid influx of calcium into the bones, causing more prolonged hypocalcemia following parathyroidectomy), acute pancreatitis, and can be drug-induced. It is also seen in critically ill patients.

Hypocalcemia varies from a mild asymptomatic biochemical abnormality to a life-threatening disorder. Acute hypocalcemia can lead to paraesthesia, tetany, and seizures. Physical signs may be observed, including Chvostek sign (twitching of muscles innervated by the facial nerve).

Symptoms from calcium elevation are typically not found unless the calcium is above 12 mg/dL. Severe hypercalcemia symptoms are more likely when calcium is >13 mg/dL. Hypercalcemia is harmful to the function of excitable membranes leading to skeletal muscle and gastrointestinal smooth muscle fatigue. Effects on cardiac muscle include a shortened QT interval and increased risk of cardiac arrest at very high calcium levels. Neurological sequelae include depression, irritability, and, with high enough levels, coma. High calcium may lead to precipitation in soft tissues such as the kidney where renal function may be severely damaged.

The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy (e.g., multiple myeloma, leukemia, lung cancer, and breast cancer). Chronic symptoms are more consistent with hyperparathyroidism, whereas recent onset of symptoms suggests malignancy (the tumor is typically very advanced). Signs and symptoms include renal stones (typical of hyperparathyroidism), lethargy, easy fatigue, depression, irritability, constipation, gastrointestinal symptoms (e.g., nausea, vomiting, abdominal pain, peptic ulcer disease, pancreatitis), polyuria, polydipsia, confusion, and coma. Hypercalcaemia may be asymptomatic.[18]

Hypomagnesemia is defined as serum magnesium <1.8 mEq/L. Serum magnesium level is a poor indicator of the total magnesium content and availability in the body because only 1% of magnesium is found in the extracellular fluid. There is no simple, rapid, and accurate laboratory test to determine total body magnesium status in humans. Magnesium deficiency can be caused by decreased magnesium intake from the diet, decreased magnesium absorption, or increased renal magnesium excretion (renal magnesium wasting). Causes include malnutrition, isolated dietary magnesium deficiency, drug-induced, alcohol abuse and pancreatitis.

Symptoms are nonspecific and include: neuromuscular irritability similar to that produced by hypocalcemia, manifesting with extensor plantar reflexes, positive Trousseau and Chvostek signs, and, in severe cases, tetany; cardiovascular features such as rapid heartbeats and an elevated blood pressure, tachycardia, and/or ventricular arrhythmias; central nervous system symptoms of vertigo, ataxia, depression, and seizure activity.

An endocrine disorder in which autonomous overproduction of parathyroid hormone (PTH) results in calcium metabolism derangement. Single parathyroid adenomas are the most common etiology (approximately 80% of cases) and familial forms are also well defined.[19] Multiple adenomas and hypertrophy of all 4 glands are less common. Diagnosis occurs through testing for a concurrent elevated serum calcium level and an inappropriately elevated intact serum PTH level. Inherited forms, affecting 10% to 20% of patients,[20] lead to hyperfunctioning parathyroid glands. Importantly, <1% of cases of hyperparathyroidism are caused by parathyroid carcinoma. In 2017, normocalcaemic primary hyperparathyroidism was recognized. It presents with high levels of PTH but with normal serum and ionized calcium levels. Some, but not all, patients will go on to develop primary hyperparathyroidism.[21]

Complications due to primary PTH are uncommon and include osteoporosis and bone fracture due to leaching of calcium from bones, and renal calculi due to elevated serum and urine calcium.

Diabetic ketoacidosis (DKA) is characterized by a biochemical triad of hyperglycemia, ketonemia, and metabolic acidosis, with rapid symptom onset. It is an acute metabolic complication of diabetes that is potentially fatal and requires prompt medical attention for successful treatment. DKA may be the first presentation of diabetes.

DKA is usually characterized by plasma glucose >250 mg/dL, arterial pH 7.0 to <7.3, and the presence of ketonemia and/or ketonuria although diagnostic criteria can vary between guidelines; see our topic Diabetic ketoacidosis for full details. Serum sodium, chloride, magnesium, and calcium are usually low; serum anion gap is elevated; and serum potassium, urea, and creatinine are usually elevated. Arterial bicarbonate ranges from <10 mEq/L in severe DKA to >15 mEq/L in mild DKA. Venous pH is recommended for monitoring treatment. Rarely, patients present with euglycemic DKA (EDKA) and have a normal blood glucose level.

Successful treatment includes correction of volume depletion, ketogenesis, hyperglycemia, electrolyte imbalances, and comorbid precipitating events, with frequent monitoring. Complications of treatment include hypoglycemia, hypokalemia, pulmonary edema, and acute respiratory distress syndrome (ARDS). Cerebral edema, a rare but potentially rapidly fatal complication, occurs mainly in children. It may be prevented by avoiding overly rapid fluid and electrolyte replacement.com.bmj.content.model.overview.Caption@6d6be8d0[Figure caption and citation for the preceding image starts]: Triad of DKAAdapted with permission from: Kitabchi AE, Wall BM. Diabetic ketoacidosis. Med Clin North Am. 1995;79:9-37 [Citation ends].

A serious metabolic complication of diabetes characterized by profound hyperglycemia (glucose >600 mg/dL), hyperosmolality (effective serum osmolality >320 mOsm/kg), and volume depletion in the absence of significant ketoacidosis (pH >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.

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.

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]

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 (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.

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