Disorders of blood chemistry may be caused by dietary factors, underlying medical conditions, and medical treatments. Resulting imbalances include acidosis (pH <7.35), alkalosis (pH >7.45), and high or low levels of key electrolyte ions, including sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), hydrogen phosphate (HPO4), and hydrogen carbonate (HCO3). 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.  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 pathophysiological approach.  
Respiratory acidosis occurs when arterial partial pressure levels of carbon dioxide (PCO2) increase to above the normal range of 4.7 to 6.0 kPa (35-45 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 recognise and treat the underlying cause can lead to respiratory failure and death. Acute respiratory acidosis (often life-threatening) is commonly caused by drug use (e.g., narcotics, alcohol, sedatives, anaesthetics), oxygen therapy in COPD, head trauma, status asthmaticus, foreign body aspiration, multilobar pneumonia, cardiogenic pulmonary oedema, pneumothorax, and inadequate mechanical ventilation. Chronic respiratory acidosis is commonly caused by obesity (both hypoventilation syndrome in obesity and impaired chest wall mobility) and COPD. Clinical features include respiratory depression (hypoventilation), obtundation, haemodynamic instability, and respiratory muscle fatigue (accessory muscle use, dyspnoea, tachypnoea).
Respiratory alkalosis is an acid-base disorder characterised by a primary reduction of PCO2 to below the normal range of 4.7 to 6.0 kPa (35-45 mmHg), leading to an increase in pH to above 7.45 and a subsequent decrease in bicarbonate (HCO3) from a normal value of 24 mmol/L (24 mEq/L). The decrease in PCO2 typically occurs as a result of alveolar hyperventilation with an excess of CO2 excretion compared to production.  The aetiologies of respiratory alkalosis are multiple and include hypoxia, parenchymal lung disease, asthma, drug effects, mechanical ventilation, central nervous system disorders, metabolic causes, pregnancy, and hyperventilation syndrome.  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 serum anion gap (SAG; calculated by subtracting the sum of major measured anions, chloride and bicarbonate, from the major measured cation, sodium). Where SAG is normal (6-12 mmol/L [6-12 mEq/L]), GI or renal causes are common.  This is also referred to as hyperchloraemic or non-anion gap metabolic acidosis. Where SAG 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 paracetamol), or salicylic acid. With simple metabolic acidosis, the normal adaptive respiratory response will decrease the arterial PCO2 1 to 1.5 times the decrease in serum HCO3. 
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 mmol/L (24 mEq/L). Causes include gastric secretion loss (e.g., vomiting, diarrhoea) and mineralocorticoid excess. Patients may present with tingling, muscle cramps, weakness, cardiac arrhythmias, and/or seizures.   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 mmol/L (<135 mEq/L); severe hyponatraemia is defined as a serum sodium <120 mmol/L (<120 mEq/L). Hyponatraemia is a common electrolyte disorder and is estimated to occur in 15% of all hospital inpatients.   With few exceptions, when the serum sodium level is low, plasma osmolality is also low (hypotonic hyponatraemia). While defined by the level of sodium, hypotonic hyponatraemia is, in fact, a disorder of water balance. Hyponatraemia is often iatrogenic and avoidable. Common causes are administration of hypotonic fluids to patients and use of thiazide diuretics (more likely to affect older people).  Hyponatraemia may also be a clue to the presence of serious underlying medical disorders. Patients who develop hyponatraemia as a result of head injury, intracranial surgery, subarachnoid haemorrhage, stroke, or brain tumours may have cerebral salt-wasting syndrome or syndrome of inappropriate antidiuretic hormone (SIADH).
Hypernatraemia is defined as a plasma sodium concentration of >145 mmol/L (>145 mEq/L). Hypernatraemia 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 hypernatraemia rarely develops. Hospitalised 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 hypernatraemia.
Hypokalaemia is a serum potassium level <3.5 mmol/L (<3.5 mEq/L). Clinical manifestations are typically seen only if the serum potassium level is <3.0 mmol/L (<3.0 mEq/L), and include muscle weakness, ECG changes, cardiac arrhythmias, rhabdomyolysis, and renal abnormalities. Hypokalaemia may result from decreased potassium intake, increased potassium entry into cells, increased potassium excretion (e.g., from the GI tract, via urine or sweat), dialysis, or plasmapheresis. Possible causes include chronic alcoholism, anorexia nervosa, hypocaloric protein diets for rapid weight loss,  metabolic or respiratory alkalosis or renal tubular acidosis, hypothermia, vomiting, severe diarrhoea,  primary aldosteronism, salt-wasting nephropathies, exercising in a hot climate,  cystic fibrosis,  hypomagnesaemia, polyuria, hypokalaemic periodic paralysis, and burns and other dermatological conditions. Some medicines can cause hypokalaemia, including diuretics, insulin treatment for diabetic ketoacidosis or nonketotic hyperglycaemia, beta-adrenergic agonists such as salbutamol or terbutaline, theophylline, chloroquine, laxative abuse or bowel-cleansing agent use, and administration of vitamin B12 or folic acid in megaloblastic anaemia. 
Hyperkalaemia (serum potassium >5.0 mmol/L [>5.0 mEq/L]) can be life-threatening and may cause cardiac arrhythmias (ventricular fibrillation) by affecting the cardiac action potential. Hyperkalaemia is often multifactorial in aetiology. 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 medicines that might increase cellular potassium release or reduce urinary excretion. Reduced potassium excretion occurs in renal failure, volume depletion, and hypoaldosteronism.  Dietary factors (e.g., excess consumption of foods high in potassium) or medicines may quickly lead to hyperkalaemia in patients with comorbidities.
Hypocalcaemia is a state of electrolyte imbalance in which the circulating serum calcium level is low. Hypocalcaemia arises mainly from either insufficient entry of calcium into the circulation or an increased loss of calcium from the circulation. Aetiologies include hypoparathyroidism, pseudohypoparathyroidism, vitamin D deficiency, magnesium imbalance, hyperphosphataemia, hungry bone syndrome, acute pancreatitis, extensive osteoblastic skeletal metastases, chelating agents (e.g., citrate, EDTA, lactate, foscarnet), drug-induced, and use of gadolinium-based MRI contrast agents. It is also seen in critically ill patients.
Symptoms from calcium elevation are typically not found unless the calcium is above 3 mmol/L (12 mg/dL). Severe hypercalcaemia symptoms and coma are likely when calcium is >3.2 mmol/L (>13 mg/dL). The most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy (e.g., multiple myeloma, leukaemia, lung cancer, and breast cancer). Chronic symptoms are more consistent with hyperparathyroidism, whereas recent onset of symptoms suggests malignancy (the tumour 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, increased risk of cardiac arrest (shortened QT interval), confusion, and coma. Hypercalcaemia may be asymptomatic. 
Hypomagnesaemia is defined as serum magnesium <0.9 mmol/L (<1.8 mEq/L). Magnesium deficiency can be caused by decreased magnesium intake from the diet, decreased magnesium absorption, or increased renal magnesium excretion (renal magnesium wasting). Symptoms are non-specific and include: neuromuscular irritability similar to that produced by hypocalcaemia, manifesting with extensor plantar reflexes, positive Trousseau's and Chvostek's signs, and, in severe cases, tetany; cardiovascular features such as rapid heartbeats and an elevated blood pressure, tachycardia, and/or ventricular arrhythmias; CNS symptoms of vertigo, ataxia, depression, and seizure activity.
An endocrine disorder in which autonomous overproduction of PTH results in calcium metabolism derangement. Single parathyroid adenomas are the most common aetiology (approximately 80% of cases) and familial forms are also well defined.  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,  lead to hyperfunctioning parathyroid glands. Importantly, <1% of cases of hyperparathyroidism are caused by parathyroid carcinoma. 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 an acute metabolic complication of diabetes that is potentially fatal and requires prompt medical attention for successful treatment. DKA may be the initial presentation in people with newly diagnosed diabetes. It is usually characterised by plasma glucose >13.9 mmol/L (>250 mg/dL), arterial pH varies from 7.0 to <7.3, and the presence of ketonaemia and/or ketonuria. Serum sodium, chloride, magnesium, and calcium are usually low, and serum anion gap (SAG; calculated by subtracting the sum of major measured anions, chloride, and bicarbonate, from the major measured cation, sodium), serum potassium, urea, and creatinine are usually elevated. Arterial bicarbonate ranges from <10 mmol/L (<10 mEq/L) in severe DKA to >15 mmol/L (>15 mEq/L) in mild DKA. Venous pH, which is usually 0.03 units lower than arterial pH, is recommended for monitoring treatment, but the difference should be noted.
A serious metabolic complication of diabetes characterised by profound hyperglycaemia (glucose >33 mmol/L [>600 mg/dL]), hyperosmolality (effective serum osmolality >320 mmol/kg [>320 mOsm/kg]), and volume depletion in the absence of significant ketoacidosis (pH >7.3 and HCO3 >15 mmol/L [>15 mEq/L]).  It is most common in older patients with type 2 diabetes. Infection is the major precipitating factor, occurring in 30% to 60% of patients. Urinary tract infections and pneumonia are the most common infections reported.  
The term 'renal tubular acidosis' (RTA) describes any one of a number of disorders in which the excretion of fixed acid (distal RTA) or the reabsorption of filtered bicarbonate (proximal RTA) is impaired to a degree disproportionate to any existing impairment of the glomerular filtration rate.  The acid retention or bicarbonate loss results in the development of hyperchloraemic metabolic acidosis marked by low serum bicarbonate and arterial blood pH. In the absence of other acid-base disorders the serum anion gap (SAG; calculated by subtracting the sum of major measured anions, chloride, and bicarbonate, from the major measured cation, sodium) is normal. Proximal and classic distal RTA are characterised by hypokalaemia.   Hyperkalaemia in distal RTA indicates that aldosterone deficiency or resistance is the cause of the problem.  There is minimal or absent urine ammonium in hyperkalaemic distal RTA. Serum sodium is usually normal. RTA is rarely symptomatic. Patients with severe acidaemia can show hyperventilation or Kussmaul's 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.
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.   This results in excessive sodium reabsorption via amiloride-sensitive epithelial sodium channels within the distal nephron, leading to hypertension and suppression of renin-AII. Urinary loss of potassium and hydrogen ions, exchanged for sodium at the distal nephron, may result in hypokalaemia and metabolic alkalosis if severe and prolonged.   This is the most common specifically treatable and potentially curable form of hypertension, accounting for at least 5% of hypertensive patients.  Most of these patients are normokalaemic.
Primary adrenal insufficiency, or Addison's 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's disease may be either acute (adrenal crisis) or insidious. The finding of low sodium and high potassium serum levels is typical. If untreated, it is a potentially life-threatening condition.
Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), facilitates free water absorption in the collecting tubule. Inappropriate secretion is characterised by hypotonic hyponatraemia, concentrated urine, and a euvolaemic state. It is primarily identified by abnormal serum sodium levels on laboratory testing, but patients may present with signs of cerebral oedema, including nausea, vomiting, headache, mental status changes, increased somnolence, or coma, and appear euvolaemic.
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