Acidosis

Resident Survival Guide

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List of terms related to Acidosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Carlos A Lopez, M.D. [2]

Overview

For acidosis referring to acidity of the urine, see renal tubular acidosis.

Acidosis is an acid-base imbalance that is an increased acidity (i.e. an increased hydrogen ion concentration). If not further qualified, it refers to acidity of the blood plasma.

Generally, acidosis is said to occur when arterial pH falls below 7.35, while its counterpart (alkalosis) occurs at a pH over 7.45. Arterial blood gas analysis and other tests are required to separate the main causes.

Strictly speaking, the term acidemia would be more appropriate to describe the state of low blood pH, reserving acidosis to describe the processes leading to these states. Nevertheless, most physicians use the terms interchangeably. The distinction may be relevant where a patient has factors causing both acidosis and alkalosis, where the relative severity of both determines whether the result is a high or a low pH.

The rate of cellular metabolic activity affects and, at the same time, is affected by the pH of the body fluids. In mammals, the normal pH of arterial blood lies between 7.35 and 7.50 depending on the species (e.g. healthy human-arterial blood pH varies between 7.35 and 7.45). Blood pH values compatible with life in mammals are limited to a pH range between 6.8 and 7.8. Changes in the pH of arterial blood (and therefore the extracellular fluid) outside this range result in irreversible cell damage (Needham, 2004).

Classification

• Acidosis can either be metabolic or respiratory.

  • Both are caused by low arterial pH.

  • Metabolic acidosis is due to an increased accumulation of acid equivalents through impairment of the regulatory ability of the liver, kidneys, or metabolism.
  • Respiratory acidosis is caused by a retention of carbon dioxide due to inadequate hypoventilation or pulmonary ventilation.

Pathophysiology

Respiratory acidosis

Respiratory acidosis results from a build-up of carbon dioxide in the blood (hypercapnia) due to hypoventilation. It is most often caused by pulmonary problems, although head injuries, drugs (especially anaesthetics and sedatives), and brain tumors can also bring it on. Emphysema, chronic bronchitis, asthma, severe pneumonia, and aspiration are among the most frequent causes. It can also occur as a response to chronic metabolic alkalosis.

Blood gases show pH below 7.35 as above mentioned, and PaCO₂ will be high (>45 mmHg / 6 kPa).

The key to distinguish between respiratory and metabolic acidosis is that in respiratory acidosis, the CO₂ is increased while the bicarbonate is either normal (uncompensated) or increased (compensated). Compensation occurs if respiratory acidosis persists for days or longer and a chronic phase is entered with partial buffering of the acidosis through renal bicarbonate retention.

Metabolic acidosis

Metabolic acidosis may result from disturbances in the ability to excrete acid via the kidneys. Renal acidosis is associated with an accumulation of urea and creatinine as well as metabolic acid residues of protein catabolism.

An increase in the production of metabolic acids may also produce metabolic acidosis. For example, lactic acidosis may occur from 1) severe (PaO2 <36mm Hg) hypoxemia causing a fall in the rate of oxygen diffusion from arterial blood to tissues, or 2) hypoperfusion (e.g. hypovolemic shock) causing an inadequate blood delivery of oxygen to tissues. A rise in lactate out of proportion to the level of pyruvate, e.g. in mixed venous blood, is termed "excess lactate" and is the best indicator of an inadequate flow of oxygen into the body's mitochondria from either cause. Oxygen debt (and muscle excess lactate) is also seen in strenuous exercise. Once oxygenation is restored, the acidosis clears quickly. Another example of increased production of acids occurs in starvation and diabetic acidosis. It is due to the accumulation of ketoacids (ketosis) and reflects a severe shift from glycolysis to lipolysis for fuel needs.

Acidic poisons, iron etc., and decreased production of bicarbonate may also produce metabolic acidosis.

Metabolic acidosis can result in stimulation of chemoreceptors and so increase alveolar ventilation, leading to respiratory compensation, otherwise known as Kussmaul breathing, which is a specific type of hyperventilation. Should this situation persist the patient is at risk for exhaustion leading to respiratory failure.

Mutations to the V-ATPase 'a4' or 'B1' isoforms result in distal renal tubular acidosis—a condition that leads to metabolic acidosis—in some cases with sensorineural deafness.

In blood gas tests, it is characterised by a low pH, low blood HCO₃, and normal or low PaCO₂. In addition to arterial blood gas one can use the anion gap to differentiate between possible causes.

The Henderson-Hasselbalch equation is useful for calculating blood pH, because blood is a buffer solution. The amount of metabolic acid accumulating can also be quantitated by using buffer base deviation, a derivative estimate of the metabolic as opposed to the respiratory component. In hypovolemic shock for example, approximately 50% of the metabolic acid accumulation is lactic acid, which disappears as blood flow and oxygen debt are corrected.

Causes

Common causes of acidosis

• Traumatic shock
• Sepsis
• Severe hypoxemia
• Severe diarrhoea
• Renal failure
• Multiple organ dysfunction syndrome
• Nausea and Vomiting
• Mesenteric insufficiency
• Ketoacidosis
• Ischemic colitis
• Hypotension
• Ethanol ingestion
• Cardiogenic shock
• Alcohol
• Acetylsalicylic acid

Causes by Organ System

Cardiovascular	Beriberi heart disease, cardiac arrest, cardiogenic shock, cardiogenic shock, cardiomyopathy, cataract and cardiomyopathy, congestive heart failure, hemorrhagic shock, hypoperfusion, hypotension, malignant hypertension, myocardial Infarction, pulseless electrical activity, pulmonary edema, shock, ST elevation myocardial infarction, torsade de pointes, ventricular arrhythmias, ventricular fibrillation
Chemical/Poisoning	Alcohol, carbon monoxide poisoning, cocaine, copperhead snake poisoning, crotalidae snake poisoning, cyanide poisoning, diethylene glycol, endothall, ethanol, ethylene glycol, germanium, isopropyl alcohol, methanol, propylene glycol, salicylate, strychnine
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Acetazolamide, acetylsalicylic acid, aspirin, biguanide, carbonic anhydrase inhibitors, didanosine, ethanol ingestion, glyburide, metformin, paracetamol, pergolide, phenformin, zalcitabine, zidovudine
Ear Nose Throat	No underlying causes
Endocrine	Adrenal cortex insufficiency, diabetes, diabetic ketoacidosis, GRACILE syndrome, hyperchloremic acidosis, hyperosmolar non-ketotic diabetic coma, hypoglycemia, ketoacidosis, permanent neonatal diabetes mellitus pheochromocytoma, thyrotoxicosis
Environmental	Drowning, hypothermic shivering
Gastroenterologic	Acute liver failure, biliary fistula, chronic mesenteric insufficiency diarrhea, fistula, hepatic failure, hepatopathy, ileus, ischemic colitis, liver disease, microvillus inclusion disease, nausea and vomiting, necrotizing enterocolitis, pancreatic fistula, severe liver disease, short bowel syndrome, small intestine fistula, volvulus
Genetic	3-alpha-hydroxyisobutyryl-CoA hydrolase deficiency, 3-Hydroxyacyl-CoA dehydrogenase II Deficiency, 3-methylglutaconic aciduria, biotinidase deficiency, coenzyme Q cytochrome c reductase deficiency, complex 1 mitochondrial respiratory chain deficiency, cystinosis, fanconi syndrome, fanconi-ichthyosis-dysmorphism, fructose-1,6-bisphosphatase deficiency, glycogen storage diseases, glutaric aciduria type 1, glutaric acidemia type 2 GRACILE syndrome, inborn urea cycle disorder, lipoamide dehydrogenase deficiency, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, medium-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, MELAS, metabolic disorders, mitochondrial DNA depletion syndrome, mitochondrial myopathy, mitochondrial neurogastrointestinal encephalopathy syndrome, multiple carboxylase deficiency, myopathy, NADH CoQ reductase deficiency, Ondine's curse, propionic acidemia, pyruvate carboxylase deficiency, pyruvate dehydrogenase phosphatase deficiency, SCHAD deficiency, sideroblastic anemia, succinic acidemia, type I glycogen storage disease, Von Gierke disease, Wilson's Disease, hydroxyacyl-coa dehydrogenase deficiency type 2, hydroxysteroid dehydrogenase deficiency, mitochondrial encephalomyopathy aminoacidopathy
Hematologic	Splenic infarction , severe anemia
Iatrogenic	No underlying causes
Infectious Disease	Sepsis, infection, fever, disseminated intravascular coagulation, clostridium difficile, cerebral malaria
Musculoskeletal/Orthopedic	No underlying causes
Neurologic	Acute disseminated encephalomyelitis, grand mal seizure, epilepsy, coma, CNS depression, cerebral hypoxia, cerebral edema
Nutritional/Metabolic	Glutaric aciduria type 1, glutaric acidemia type 2, total parenteral nutrition, starvation
Obstetric/Gynecologic	No underlying causes
Oncologic	Tumor, myeloma, lymphoma, leukemia
Ophthalmologic	No underlying causes
Overdose/Toxicity	Toluene, Salicylates, ethylene glycol, ethanol ingestion, alcohol, isopropyl alcohol, diethylene glycol
Psychiatric	No underlying causes
Pulmonary	Status asthmaticus, severe asthma, pulmonary embolism, infant respiratory distress syndrome, hypercapnia, following chronic hyperventilation CO2 intoxication, chronic obstructive lung disease, apnea, acute respiratory distress syndrome
Renal/Electrolyte	Hypoaldosteronism, hypokalemic distal renal tubular acidosis, hyperkalemic distal renal tubular acidosis, kidney disorders, proximal renal tubular acidosis, renal tubular acidosis, renal failure, renal circulatory insufficiency, hyperkalemia, distal renal tubular acidosis, decreased renal acid excretion, chronic kidney disease, chronic interstitial nephritis, acute renal failure, acute glomerulonephritis
Rheumatology/Immunology/Allergy	No underlying causes
Sexual	No underlying causes
Trauma	Traumatic shock
Urologic	Ureterosigmoidostomy, urinary diversion
Miscellaneous	Hypoxia, hypovolemia , heavy physical work, fistula, enhanced metabolic rate, diet

Causes in Alphabetical Order

• 3-alpha-hydroxyisobutyryl-CoA hydrolase deficiency
• 3-Hydroxyacyl-CoA dehydrogenase II Deficiency
• 3-methylglutaconic aciduria
• Acetazolamide
• Acetylsalicylic acid
• Acute disseminated encephalomyelitis
• acute glomerulonephritis
• Acute liver failure
• Acute renal failure
• Acute respiratory distress syndrome
• Adrenal cortex insufficiency
• Alcohol
• Apnea
• Aspirin
• Beriberi heart disease
• Biguanide
• Biliary fistula
• Biotinidase deficiency
• Carbon monoxide poisoning
• Carbonic anhydrase inhibitors
• Cardiac arrest
• Cardiogenic shock
• Cardiomyopathy
• Cataract and cardiomyopathy
• Cerebral edema
• Cerebral hypoxia
• Cerebral malaria
• Chronic interstitial nephritis
• Chronic kidney disease
• Chronic mesenteric insufficiency
• Chronic obstructive lung disease
• Clostridium difficile
• CNS depression
• Cocaine
• Coenzyme Q cytochrome c reductase deficiency
• Coma
• Complex 1 mitochondrial respiratory chain deficiency
• Congestive heart failure
• Copperhead snake poisoning
• Crotalidae snake poisoning
• Cyanide poisoning
• Cystinosis
• Decreased renal acid excretion
• Diabetes
• Diabetic ketoacidosis
• Diarrhea
• Didanosine
• Diethylene glycol
• Disseminated intravascular coagulation
• Distal renal tubular acidosis
• Drowning
• Endothall
• Epilepsy
• Ethanol
• Ethylene glycol
• Fanconi syndrome
• Fanconi-ichthyosis-dysmorphism
• Fever
• Fistula
• Fructose-16-bisphosphatase deficiency
• Germanium
• Glutaric acidemia type 2
• Glutaric aciduria type 1
• Glyburide
• Glycogen storage diseases
• GRACILE syndrome
• Grand mal seizure
• Hemorrhagic shock
• Hepatic failure
• Hepatopathy
• Hydroxyacyl-coa dehydrogenase deficiency type 2
• Hydroxysteroid dehydrogenase deficiency
• Hypercapnia
• Hyperchloremic acidosis
• Hyperkalemia
• Hyperosmolar non-ketotic diabetic coma
• Hypoaldosteronism
• Hypoglycemia
• Hypokalemic distal renal tubular acidosis
• Hypoperfusion
• Hypothermic shivering
• Ileus
• Inborn urea cycle disorder
• Infant respiratory distress syndrome
• Infection
• Ischemic colitis
• Isopropyl alcohol
• Ketoacidosis
• Kidney disorders
• Leukemia
• Lipoamide dehydrogenase deficiency
• Liver disease
• Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
• Lymphoma
• Malignant hypertension
• Medium-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
• MELAS
• Metabolic disorders
• Metformin
• Methanol
• Microvillus inclusion disease
• Mitochondrial DNA depletion syndrome
• Mitochondrial encephalomyopathy aminoacidopathy
• Mitochondrial myopathy
• Mitochondrial neurogastrointestinal encephalopathy syndrome
• Multiple carboxylase deficiency
• Myeloma
• Myocardial Infarction
• Myopathy
• NADH CoQ reductase deficiency
• Necrotizing enterocolitis
• Ondine's curse
• Pancreatic fistula
• Paracetamol
• Pergolide
• Permanent neonatal diabetes mellitus
• Phenformin
• Pheochromocytoma
• Propionic acidemia
• Propylene glycol
• Proximal renal tubular acidosis
• Pulmonary edema
• Pulmonary embolism
• Pulseless electrical activity
• Pyruvate carboxylase deficiency
• Pyruvate dehydrogenase phosphatase deficiency
• Renal circulatory insufficiency
• Renal failure
• Renal tubular acidosis
• Salicylate
• Salicylates
• SCHAD deficiency
• Sepsis
• Severe liver disease
• Shock
• Short bowel syndrome
• Sideroblastic anemia
• Small intestine fistula
• ST elevation myocardial infarction
• Starvation
• Status asthmaticus
• Strychnine
• Succinic acidemia
• Thyrotoxicosis
• Toluene
• Torsade de pointes
• Total parenteral nutrition
• Tumor
• Type I glycogen storage disease
• Ureterosigmoidostomy
• Urinary diversion
• Ventricular arrhythmias
• Ventricular fibrillation
• Volvulus
• Vomiting
• Von Gierke disease
• Wilson's Disease
• Zalcitabine
• Zidovudine

Respiratory Acidosis

Amyotrophic Lateral Sclerosis (ALS) Botulism Brainstem injury or infarction Bronchospasm Cerebral injury or infarction Chest trauma Congestive heart failure Diaphragmatic paralysis Drugs, toxins Familial periodic paralysis Guillain-Barré syndrome High spinal cord injury Hypochloremic Acidosis Hypokalemic myopathy Inadequate mechanical ventilation Kyphoscoliosis

Laryngeal spasm or edema Muscular Dystrophy Myasthenia Gravis Neoplasm Pneumonia Pneumothorax Poliomyelitis Polyradiculitis Primary hypoventilation Pulmonary edema Pulmonary embolism Respiratory Distress Syndrome Restrictive Lung Disease Sleep Apnea Smoke inhalation Tetanus Tracheal stenosis or edema

Treatment

Treatment of any of the varieties of metabolic acidosis is focused upon correction of the underlying problem. However, neutralizing the acidosis with infusions of bases like sodium bicarbonate may be temporarily helpful in some critical emergencies.

External Links

• National Kidney and Urologic Diseases Information Clearinghouse