Question

    Acidosis (Acidoses)

    Acidosis is the condition of having too much acid in the blood and other body fluids with two classifications – metabolic acidosis or respiratory acidosis.

    Acidosis is caused by the following process: biochemical.

    Presentation

    Metabolic acidosis
    The signs will depend on the underlying cause. Usually there will be a rapid breathing (tachypnoea), lethargy and confusion with a headache. Severe disease can progress to shock or death. There is a fruity smell from the ketones of diabetic acidosis [6].

    Respiratory acidosis:
    Presenting signs can include lethargy or fatigue, shortness of breath, confusion and sleepiness [7].

    neurologic
    Altered Mental Status
    • In more severe cases it can present with altered mental status, coma, hypotension, hypothermia and respiratory insufficiency.[calpoison.org]
    Confusion
    • These include rapid breathing, lethargy, tiredness, headaches and confusion.[symptoma.com]
    • If you develop severe metabolic acidosis, you will likely experience drowsiness and extreme weakness, as well as increased nausea and confusion, Merck Manuals note.[livestrong.com]
    • People with respiratory acidosis often have headache and confusion, and breathing may appear shallow, slow, or both.[merckmanuals.com]
    • Confusion or lethargy may also occur.[nlm.nih.gov]
    • According to other sources, symptoms of mild hypercapnia might include headache, confusion and lethargy.[en.wikipedia.org]
    Lethargy
    • These include rapid breathing, lethargy, tiredness, headaches and confusion.[symptoma.com]
    • Confusion or lethargy may also occur.[nlm.nih.gov]
    • Seek immediate medical care (call 911) for serious symptoms, such as rapid breathing, confusion, shortness of breath, and lethargy, especially in the setting of lung disease, kidney disease, or other diseases that can cause acidosis.[healthgrades.com]
    • Sub-acute : Reduced feed intake Poor body condition and weight loss Unexplained diarrhoea Temperature Pulse rate and respiratory rate may rise Lethargy Treatment Because subacute ruminal acidosis is not detected at the time of depressed ruminal pH, there[thecattlesite.com]
    • Other symptoms for lactic acidosis include: Nausea Vomiting Abdominal pain Lethargy Abnormal breathing Low blood pressure Irregular heart rhythm Causes of Lactic Acidosis Lactic Acidosis is caused if a person reaches the anaerobic threshold or lactate[acidalkalinediet.net]
    Stupor
    • In respiratory acidosis, the earliest symptoms are Drowsiness may progress to stupor and coma as the oxygen in the blood becomes inadequate.[merckmanuals.com]
    • As the acid level goes up these symptoms progress to stupor, unconsciousness, coma, and death.[medical-dictionary.thefreedictionary.com]
    • Examination Lethargy, stupor and progression to a state of coma may occur, particularly in cases of poisoning.[patient.info]
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  • respiratoric
    Hyperpnea
    • Symptoms and signs in severe cases include nausea and vomiting, lethargy, and hyperpnea.[merckmanuals.com]
    Kussmaul Respiration
    • […] characterized by hydrogen (H ) ion increase or base (OH - ) loss, so that the tissue pH can no longer be maintained at 7.4 metabolic acidosis acidosis caused by ketone body accumulation; characterized by diarrhoea, vomiting and dehydration and hyperventilation (Kussmaul[medical-dictionary.thefreedictionary.com]
    • Kussmaul's respiration may be noted where there is deep, slowly rhythmic breathing that increases the minute tidal volume.[patient.info]
    Tachypnea
    • Tachypnea in physiological response to metabolic acidosis can be an early sign.[calpoison.org]
    • The clinical signs usually indicate reduced tissue perfusion and include severe hypotension, tachypnea, oliguria or anuria, peripheral vasoconstriction and deteriorating mental status.[fitsweb.uchc.edu]
    • Signs and symptoms [ edit ] Symptoms and signs of early hypercapnia include flushed skin, full pulse , tachypnea , dyspnea , extrasystoles , muscle twitches, hand flaps, reduced neural activity, and possibly a raised blood pressure .[en.wikipedia.org]
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  • gastrointestinal
    Nausea
    • If you develop severe metabolic acidosis, you will likely experience drowsiness and extreme weakness, as well as increased nausea and confusion, Merck Manuals note.[livestrong.com]
    • Typical symptoms can be fairly nebulous and include abdominal pain, nausea, vomiting, malaise, myalgia and dizziness.[calpoison.org]
    • People with metabolic acidosis often have nausea, vomiting, and fatigue and may breathe faster and deeper than normal.[msdmanuals.com]
    • Symptoms of acidosis are: fast, deep breathing a smell of acetone on your breath nausea and vomiting stomach pains.[netdoctor.co.uk]
    • Other symptoms for lactic acidosis include: Nausea Vomiting Abdominal pain Lethargy Abnormal breathing Low blood pressure Irregular heart rhythm Causes of Lactic Acidosis Lactic Acidosis is caused if a person reaches the anaerobic threshold or lactate[acidalkalinediet.net]
    Vomiting
    • Metabolic acid-base disorders may be due to kidney disease , electrolyte disturbances, severe vomiting or diarrhea, ingestion of certain drugs and toxins, and diseases that affect normal metabolism (e.g., diabetes ).[labtestsonline.org]
    • Vomiting causes metabolic alkalosis because a lot of stomach acid is lost when someone vomits, and this leads to the reduction of acidity within the body.[study.com]
    • Symptoms of acidosis are: fast, deep breathing a smell of acetone on your breath nausea and vomiting stomach pains.[netdoctor.co.uk]
    • People with metabolic acidosis often have nausea, vomiting, and fatigue and may breathe faster and deeper than normal.[msdmanuals.com]
    • The Merck Manuals list symptoms of mild metabolic acidosis that include fatigue, nausea, vomiting, and an increase in breathing rate and depth that occur when your body tries to counter the effects of acidosis by purging carbon dioxide.[livestrong.com]
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  • cardiovascular
    Tachycardia
    • Cardiac telemetry monitoring showed a narrow complex sinus tachycardia.[calpoison.org]
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  • Workup

    A full history and a thorough clinical examination will allow a correct diagnosis.

    Laboratory support will provide extra information with arterial blood gas analyses and electrolyte analysis with a basic metabolic panel. These will confirm the acidosis and identify whether it is metabolic or respiratory in origins [8].

    Laboratory

    Serum
    Lactate Decreased
    • Lactic acidosis results from overproduction of lactate, decreased metabolism of lactate, or both.[merckmanuals.com]
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  • Urine
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  • ECG

    QT, RR, ST Intervals
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  • Treatment

    The mainstay of treatment is the use of appropriate fluid therapy using either oral or intravenous routes.

    Sodium acetate may be used specifically to neutralise the acids.

    At the same time the underlying cause must be treated.

    In the most severe cases, severe measures such as mechanical ventilation or liver transplantation may be indicated [9].

    Prognosis

    The prognosis is generally favourable if prompt treatment is initiated. However, complications depend on the underlying cause.

    Complications

    Cardiac Arrhythmia
    • Low plasma potassium levels in those with the classic form of dRTA can also cause cardiac arrhythmias, paralysis and even death.[orpha.net]
    • In mild cases the symptoms may be overlooked; in severe cases symptoms are more obvious and may include muscle twitching, involuntary movement, cardiac arrhythmias, disorientation, and coma.[medical-dictionary.thefreedictionary.com]
    • If pH is 7.1-7.2 then cardiac arrhythmias are likely.[patient.info]
    • Conversely, the literature is extensive on targeting of the pathophysiology of metabolic acidosis in cardiac arrhythmias, mainly in ischemia-reperfusion models.[ccforum.biomedcentral.com]
    Hypercapnia
    • Hypercapnia can induce increased cardiac output, an elevation in arterial blood pressure, and a propensity toward arrhythmias . [4] [5] Hypercapnia may increase pulmonary capillary resistance. [ citation needed ] In severe hypercapnia (generally PaCO[en.wikipedia.org]
    • Alveolar hypoventilation leads to an increased PaCO 2 (ie, hypercapnia).[emedicine.medscape.com]
    • It is completed within 5-10 min from onset of hypercapnia. b.[slideshare.net]
    • Hypercapnia only occurs if severe disease or respiratory muscle fatigue occurs.[en.wikipedia.org]
    • Respiratory acidosis results from a build-up of CO 2 in the blood (hypercapnia) due to hypoventilation.[boundless.com]
    Hyperkalemia
    • When this process is abnormal, it can cause too much potassium to build up in the blood ( hyperkalemia ).[kidshealth.org]
    • Failure ACE Inhibitor Renin Deficiency Aging Extracellular fluid volume expansion Lead Beta Blocker s Prostaglandin Inhibitor Methyldopa Carbonic anhydrase inhibitor Acetazolamide Mefenamic acid Post-hypocapnia Excessive Normal Saline infused (liters) Hyperkalemia[fpnotebook.com]
    • In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia .[en.wikipedia.org]
    • Renal HCO 3 loss Tubulointerstitial renal disease Renal tubular acidosis, types 1, 2, and 4 Hyperparathyroidism Acetazolamide Parenteral infusion Arginine Lysine Ammonium chloride (NH 4 Cl) Rapid sodium chloride (NaCl) infusion Other Hypoaldosteronism Hyperkalemia[merckmanuals.com]
    • Due to its toxicity (hyperkalemia), its usefulness in the critical care setting is reduced in instances of significant renal impairment with a glomerular filtration rate under 30 ml.minute 1 .[ccforum.biomedcentral.com]
    Hyperventilation
    • Previous Index Next 5.5.1 Hyperventilation Compensation for a metabolic acidosis is hyperventilation to decrease the arterial pCO 2 .[anaesthesiamcq.com]
    • A notable exception is the patient with the anxiety-hyperventilation syndrome; in addition to reassurance or sedation, rebreathing into a closed system (e.g., a paper bag) might prove helpful by interrupting the vicious cycle that can result from the[slideshare.net]
    • Kussmaul hyperventilation (deep sighing respiration) may be observed if the severity of the acidosis is sufficient to elicit a degree of respiratory compensation.[fitsweb.uchc.edu]
    • Hyperventilation may occur as a result of stimulation of the hypothalamus. blood gas analysis will reveal a lowered pH and an elevated Pa CO 2 .[medical-dictionary.thefreedictionary.com]
    • It can be due to: Electrolyte disturbances caused by, for example, prolonged vomiting or severe dehydration Administration or consumption of base Hyperventilation (with increased excretion of acid in the form of CO 2 ) Any disease or condition that affects[labtestsonline.org]
    Hypocapnia
    • It is completed within 5-10 min from onset of hypocapnia b.[slideshare.net]
    • A failure of this reflex can be fatal, for example as a contributory factor in sudden infant death syndrome . [1] Hypercapnia is the opposite of hypocapnia , the state of having abnormally reduced levels of carbon dioxide in the blood.[en.wikipedia.org]
    • Often these diseases stimulate ventilation and hypocapnia due to reflex receptors and hypoxia.[emedicine.medscape.com]
    • Mineralocorticoid Deficiency Angiotensin Deficiency: Liver Failure ACE Inhibitor Renin Deficiency Aging Extracellular fluid volume expansion Lead Beta Blocker s Prostaglandin Inhibitor Methyldopa Carbonic anhydrase inhibitor Acetazolamide Mefenamic acid Post-hypocapnia[fpnotebook.com]
    • Lung diseases that primarily cause abnormality in alveolar gas exchange usually do not cause hypoventilation but tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia.[en.wikipedia.org]
    Hypotension
    • Hypotension may make hemodialysis a challenging endeavor.[calpoison.org]
    • Some weeks or months (in one case) after starting this therapy they suddenly became critically ill with severe hypotension, renal failure and rapidly deteriorating neurological state.[acutecaretesting.org]
    • The clinical signs usually indicate reduced tissue perfusion and include severe hypotension, tachypnea, oliguria or anuria, peripheral vasoconstriction and deteriorating mental status.[fitsweb.uchc.edu]
    • Severe, acute acidemia predisposes to cardiac dysfunction with hypotension and shock, ventricular arrhythmias, and coma.[merckmanuals.com]
    • CAUSES… Hypoxemia or tissue hypoxia Decreased inspired O2 tension/High altitude Bacterial or viral pneumonia Aspiration of food, foreign body, or vomitus Larygospasm, Drowning Cyanotic heart disease, Severe ciurculatory failure Severe anemia,Hypotension[slideshare.net]
    Ketosis
    • Causes: Metabolic Acidosis and Elevated Osmolal Gap Toxic Alcohol ingestion Eythylene glycol Methanol Serum K etone increase (ketosis) Alcohol ic ketoacidosis Diabetic Ketoacidosis VI.[fpnotebook.com]
    • It is due to the accumulation of ketoacids (ketosis) and reflects a severe shift from glycolysis to lipolysis for energy needs.[boundless.com]
    • It is due to the accumulation of ketoacids (via excessive ketosis) and reflects a severe shift from glycolysis to lipolysis for energy needs.[en.wikipedia.org]
    • If they are present in moderate or heavy amounts, ketosis is present and acidosis is likely to occur a blood sample taken from an artery – this is done in hospital and accurately measures the acidity of the blood.[netdoctor.co.uk]
    • In addition, blood and tissue acid-base balance is further complicated during ketosis.[sportsci.org]
    Osteomalacia
    • Failure to thrive, rickets, stunting of growth (seen in children) and osteomalacia or osteopenia (seen in adults) are a result of urinary calcium wastage and a loss of calcium salts from the bones.[orpha.net]
    • Chronic acidemia causes bone demineralization disorders (eg, rickets, osteomalacia, osteopenia).[merckmanuals.com]
    Shock
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  • Etiology

    Acidosis occurs when the pH (hydrogen ion concentration) of blood plasma falls below 7.35.

    1. Respiratory acidosis (also known as hypercapnic acidosis) is the result of too much carbon dioxide remaining in the body because inadequate amounts are being removed by breathing.
    2. Metabolic acidosis occurs when either too much acid is produced in the body or too little is removed by the kidneys [2].

    Epidemiology

    1. Respiratory acidosis can be caused by inadequate respiratory function for several underlying reasons -

    2. Several different forms of metabolic acidosis can occur with several various types of underlying pathology:

    Lactic acidosis occurs as a result of the build-up of lactic acid -

    Diabetic acidosis (also known as diabetic ketoacidosis – DKA) occurs as a result of the accumulation of acidic ketone bodies during uncontrolled diabetes mellitus.

    Hyperchloraemic acidosis occurs with the loss of sodium bicarbonate from the body, e.g. sever diarrhoea or vomiting.

    Other reasons for metabolic acidosis include – [3]

    Sex distribution
    Age distribution

    Pathophysiology

    Metabolic acidosis can either be caused when there is inadequate removal of excessive metabolicacids by the kidneys or over-production of metabolic acids elsewhere in body by other disturbed systems. These latter include urea and creatinine as well as the metabolic residues of protein catabolism. Overproduction of lactic acid can occur with excessive exercise or as a result of hypoxia in tissues with poor blood perfusion or low blood oxygen levels [4].
    Stimulation of chemoreceptors by the raised acid levels leads to increased alveolar ventilation and results in some compensation for metabolic acidosis by the lungs with increased carbon dioxide exhalation. This alters the body’s buffering system to further reduce the metabolic acidosis.

    Respiratory acidosis is usually the result of ineffective breathing and to return this back to a normal condition it will usually be useful to reverse the acidosis. However, where there is severe disturbance, e.g. trauma or nerve paralyses, mechanical ventilation may be needed as well [5].

    Prevention

    Mechanisms for prevention depend on the underlying cause. Metabolic acidosis can be prevented by ensuring the proper management of the underlying causes, e.g hepatic, renal and diabetic disease as well as avoiding excessive exercise or dehydration [10].

    Summary

    Normally the kidneys and the lungs maintain the balance between acids and bases in the body as part of homoeostasis so that the level of acidity (pH) is maintained within a narrow range – about 7.4. When either the acids build up or the bicarbonate (base) is lost, acidosis develops [1].

    Patient Information

    Definition: Acidosis is a buildup of acids in the body so that the pH of the blood plasma falls below 7.35


    Cause: There are two types of acidosis depending on the underlying cause.

    1. Metabolic acidosis - in which the kidneys are unable to effectively remove the acids produced by the body’s metabolism or in which the body is over-producing certain acids so that normal mechanisms can no longer maintain the level of hydrogen ions within the normal range. Potential causes include uncontrolled diabetes, over-exercise, poor diet, dehydration, overuse of drugs, diseases of the kidney and liver.


    2. Respiratory acidosis results from the inability of the lungs to effectively remove carbon dioxide from the body. Changes in the lung ventilation may be caused by such chronic diseases as asthma, chest deformities, cancer, trauma to the chest or altered nerve function.


    Symptoms: The symptoms of acidosis are similar for both the respiratory and metabolic forms. These include rapid breathing, lethargy, tiredness, headaches and confusion.

    Diagnosis: Clinical signs and history should allow the underlying identification. Analysis of blood samples supported by a basic metabolic panel will provide an electrolyte analysis, while arterial blood gas analysis will conform the acidosis and identify whether this is metabolic or respiratory in origins.

    Treatment: Fluid therapy with appropriate solutions, either oral or intravenous, will be used to correct the acidosis. Sometimes sodium acetate is used separately to neutralize the acids. Correcting the underlying problem is also important. Sometime mechanical ventilation is needed to correct severe respiratory acidosis.

    Prevention: Correct management of the disease is critical to prevention its further development. Examples include controlling diabetes and avoiding excessive exercise or severe weather that might lead to dehydration.

    Self-assessment

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    References

    1. Winter SD, Pearson JR, Gabow PA, et al. The fall of the serum anion gap. Arch Intern Med 1990; 150:311.
    2. Morimatsu H, Toda Y, Egi M, et al. Acid-base variables in patients with acute kidney injury requiring peritoneal dialysis in the pediatric cardiac care unit. J Anesth. 2009;23(3):334-40.
    3. Fernandez PC, Cohen RM, Feldman GM. The concept of bicarbonate distribution space: the crucial role of body buffers. Kidney Int 1989; 36:747.
    4. Pereira PC, Miranda DM, Oliveira EA, Silva AC. Molecular pathophysiology of renal tubular acidosis. Curr Genomics. Mar 2009;10(1):51-9
    5. Corey HE. Stewart and beyond: new models of acid-base balance. Kidney Int 2003; 64:777.
    6. Kraut JA, Kurtz I. Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment. Am J Kidney Dis 2005; 45:978.
    7. Ehrsam RE, Heigenhauser GJ, Jones NL. Effect of respiratory acidosis on metabolism in exercise. J Appl Physiol. Jul 1982;53(1):63-9.
    8. Wiseman AC, Linas S. Disorders of potassium and acid-base balance. Am J Kidney Dis. May 2005;45(5):941-9
    9. Pierce NF, Fedson DS, Brigham KL, et al. The ventilatory response to acute base deficit in humans. Time course during development and correction of metabolic acidosis. Ann Intern Med 1970; 72:633.
    10. Adrogué HJ, Eknoyan G, Suki WK. Diabetic ketoacidosis: role of the kidney in the acid-base homeostasis re-evaluated. Kidney Int 1984; 25:591.

    • Bicarbonate therapy for dysrhythmia and hypotension in tricyclic antidepressant overdose. - JR Hoffman, CR McElroy - Western Journal of Medicine, 1981 - ncbi.nlm.nih.gov
    • ASRA practice advisory on local anesthetic systemic toxicity - JM Neal, CM Bernards, JF Butterworth IV - anesthesia and pain , 2010 - journals.lww.com
    • Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma - S Blüher, M Schulz, U Bierbach - European journal of , 2008 - Springer
    • 21 Neuroleptic Malignant Syndrome - CL Chen - Anish Bhardwaj, MD Marek A. Mirski, MD, PhD John A , 2004 - books.google.com
    • Acidosis occurring with diarrhea - J Howland, WMK Marriott - Archives of Pediatrics & Adolescent , 1916 - Am Med Assoc
    • A clinical and laboratory profile of Cleistanthus collinus poisoning - DKS Subrahmanyam, T Mooney, R Raveendran - OF PHYSICIANS OF , 2003 - japi.org
    • Aortic pressure during human cardiac arrest. Identification of pseudo-electromechanical dissociation. - NA Paradis, GB Martin, MG Goetting, EP Rivers - , 1992 - chestjournal.chestpubs.org
    • Acetaminophen and salicylate serum levels in patients with suicidal ingestion or altered mental status - KA Sporer, H Khayam-Bashi - The American journal of emergency , 1996 - Elsevier
    • Channelopathies: Brugada syndrome, long QT syndrome, short QT syndrome, and CPVT - R Schimpf, C Veltmann, C Wolpert, M Borggrefe - Herz, 2009 - Springer
    • A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context - R Geddes, S Knight, MYS Moosa, A Reddi - South African Medical , 2008 - samj.org.za
    • Acute renal failure in patients with severe falciparum malaria - TTM Trang, NH Phu, H Vinh, TT Hien - Clinical infectious , 1992 - cid.oxfordjournals.org
    • A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children - E Isolauri, T Rautanen, M Juntunen, P Sillanaukee - Pediatrics, 1991 - Am Acad Pediatrics
    • Acetazolamide in the treatment of seizures - WG Reiss, KS Oles - The Annals of pharmacotherapy, 1996 - Harvey Whitney Books
    • 'Classical'organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: Long-term outcome and effects of expanded newborn screening using - C Dionisi-Vici, F Deodato, W Röschinger - Journal of inherited , 2006 - Springer
    • A case study in metabolic induced by inhalation - T Stover-Wall - Air Medical Journal, 2005 - Elsevier
    • Results in metabolic acidosis and energy failure in cerebellar granule cells: an in vitro model for the study of cell death mechanisms in Wernicke's encephalopathy - P Pannunzio, AS Hazell, M Pannunzio - Journal of , 2000 - Wiley Online Library
    • Be used as a first-line drug for cardiopulmonary arrest (CPA)?: comparative study of out-of-hospital CPA with acidosis and in-hospital CPA without acidosis. - K Yoshioka, M Amino, S Morita, Y Nakagawa - journal: official journal , 2006 - ukpmc.ac.uk
    • D-lactic acidosis: pathologic consequence of saprophytism - A Vella, G Farrugia - Mayo Clinic Proceedings, 1998 - Elsevier
    • A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y - D Leigh, PN Bowers, Q Liu, T Morgan, T Zhang - J Clin , 2006 - Am Soc Clin Investig
    • Etiologic organisms as independent predictors of death and morbidity associated with bloodstream infections - PJ Miller, RP Wenzel - Journal of Infectious Diseases, 1987 - jid.oxfordjournals.org
    • A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. - EA Koller, J Weber, PM Doraiswamy - The Journal of clinical , 2004 - ukpmc.ac.uk
    • A randomized, double-blind, placebo-controlled study of verapamil and metoprolol in treatment of multifocal atrial tachycardia - E Arsura, AS Lefkin, DL Scher, M Solar - The American Journal of , 1988 - Elsevier
    • Bupivacaine-induced cardiac arrhythmias in sheep. - DM Kotelko, SM Shnider, PA Dailey, RV Brizgys - Anesthesiology, 1984 - ukpmc.ac.uk
    • Acute cocaine poisoning: Importance of treating seizures and acidosis - S Jonsson, M O'Meara, JB Young - The American journal of medicine, 1983 - Elsevier
    • Acute organic brain syndrome: a review of 100 cases - FR Purdie, B Honigman, P Rosen - Annals of Emergency Medicine, 1981 - Elsevier
    • A 16-day-old breast-fed infant with metabolic acidosis caused by salicylate - JH Clark, WG Wilson - Clinical pediatrics, 1981 - cpj.sagepub.com
    • A Specific Form of Renal Acidosis, the Therapeutic Indications for Each Etiological Sub-Group, and the Relationship Between Osteomalacia and Milkman's Syndrome - F Albright, CH BURNETT, W Parson - Medicine, 1946 - journals.lww.com

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