Find information on thousands of medical conditions and prescription drugs.

Metabolic acidosis

In medicine, metabolic acidosis is a state in which the blood pH is low (under 7.35) due to increased production of H+ by the body or the inability of the body to form bicarbonate (HCO3-) in the kidney. Its causes are diverse, and its consequences can be serious, including coma and death. Together with respiratory acidosis, it is one of the two general types of acidosis. more...

Mac Ardle disease
Macular degeneration
Mad cow disease
Maghazaji syndrome
Mal de debarquement
Malignant hyperthermia
Mallory-Weiss syndrome
Malouf syndrome
Marburg fever
Marfan syndrome
MASA syndrome
Mast cell disease
MAT deficiency
Maturity onset diabetes...
McArdle disease
McCune-Albright syndrome
Mediterranean fever
Megaloblastic anemia
Meleda Disease
Meniere's disease
Mental retardation
Mercury (element)
Metabolic acidosis
Metabolic disorder
Methylmalonic acidemia
Microscopic polyangiitis
Microtia, meatal atresia...
Miller-Dieker syndrome
Mitochondrial Diseases
Mitral valve prolapse
Mobius syndrome
MODY syndrome
Moebius syndrome
Molluscum contagiosum
MOMO syndrome
Mondini Dysplasia
Mondor's disease
Monoclonal gammopathy of...
Morquio syndrome
Motor neuron disease
Moyamoya disease
MPO deficiency
Mullerian agenesis
Multiple chemical...
Multiple endocrine...
Multiple hereditary...
Multiple myeloma
Multiple organ failure
Multiple sclerosis
Multiple system atrophy
Muscular dystrophy
Myalgic encephalomyelitis
Myasthenia gravis
Mycosis fungoides
Myelodysplastic syndromes
Myeloperoxidase deficiency
Myoadenylate deaminase...
Myositis ossificans

Signs and symptoms

Symptoms are aspecific, and diagnosis can be difficult unless the patient presents with clear indications for arterial blood gas sampling. Symptoms may include chest pain, palpitations, headache, altered mental status, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite (either anorexia or excessive eating) and weight loss (longer term), muscle weakness and bone pains. A slightly specific finding is when the patient reports rapid breathing, not due to shortness of breath but an unmotivated drive to hyperventilate. Kussmaul respiration is rare, but may indicate ketoacidosis.

Exteme acidosis leads to neurological and cardiac complications:

  • Neurological: lethargy, stupor, coma, seizures.
  • Cardiac: arrhythmias (ventricular tachycardia), decreased response to epinephrine; both lead to hypotension (low blood pressure).

Physical examination occasionally reveals signs of disease, but is otherwise normal. Cranial nerve abnormalitites are reported in ethylene glycol poisoning, and retinal oedema can be a sign of methanol (methyl alcohol) intoxication. Longstanding chronic metabolic acidosis leads to osteoporosis and can cause fractures.


Arterial blood gas sampling is essential for the diagnosis. The pH is low (under 7.35) and the bicarbonate levels are decreased (<12 mmol/l). In respiratory acidosis (low blood pH due to decreased clearance of carbon dioxide by the lungs), the bicarbonate is elevated, due to increased conversion from H2CO3. An ECG can be useful to anticipate cardiac complications.

Other tests that are relevant in this context are electrolytes (including chloride), glucose, renal function and a full blood count. Urinalysis can reveal acidity (salicylate poisoning) or alkalinity (renal tubular acidosis type I). In addition, it can show ketones in ketoacidosis.

To distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is considered very useful. It is calculated by subtracting the chloride and bicarbonate levels from the sodium plus potassium levels.

Anion gap = ( + ) - ( + )

As sodium and potassium are the main extracellular cations, and chloride and bicarbonate are the main anions, the result should reflect the remaining anions. Normally, this concentration is about 8-16 mmol/l. An elevated anion gap (i.e. > 16 mmol/l) can indicate particular types of metabolic acidosis, particularly certain poisons, lactate acidosis and ketoacidosis.

As the differential diagnosis is narrowed down, certain other tests may be necessary, including toxicological screening and imaging of the kidneys.


[List your site here Free!]

Metabolic acidosis and renal tubular injury due to pure toluene inhalation
From Archives of Environmental Health, 9/1/94 by Michihiro Kamijima

TOLUENE is an ubiquitous solvent in industry and is easily obtainable. Habitual inhalation of thinner containing toluene remains one of the conspicuous problems of young generations in Japan. It is also important from the viewpoint of occupational health to study health disorders of thinner sniffers. Metabolic acidosis associated with thinner sniffing is not as common as are symptoms of the central nervous system. Taher et al. first reported two cases of renal tubular acidosis (RTA) after sniffing of toluene-containing substances in 1974.[1] The relation between acidosis and the inhalation of toluene has been established by similar cases reported subsequent to the publication of the study by Taher et al.[2-10]

The mechanism by which acidosis results from toluene inhalation is not elucidated. Not only impaired urinary acidification, but accumulation of toluene metabolites has been discussed.[2-4,9,11] Though Batlle et al. evaluated urinary acidification and hippuric acid levels systematically in several toluene sniffers,[9] histopathological information remains insufficient. We report here the histopathological changes of a case of metabolic acidosis resulting from pure toluene inhalation.

Case report

A 22-y-old woman was admitted on the night of July 6, 1992, with weakness and unsteadiness of her lower extremities. The patient was healthy and had no abnormal urinary findings throughout her childhood. She first sniffed glue at the age of 16 and began sniffing thinner when she was 18. in 1989, at the age of 19, she was admitted for weight loss and hepatorenal dysfunction. She made a rapid recovery. Renal biopsy disclosed no pathological changes at that time. She resumed sniffing thinner in April, 1992, and inhaled about two or three times a week until May, after which, in June, she inhaled more than twice a day. Her method was to drip thinner into a plastic-film bag, inflate the bag, and inhale the air in it repeatedly. The thinner left in the patient's room was more than 99 w/w% toluene, and its concentration in a plastic-film bag at 26 [degree] C was 22 700 ppm. At the end of June, she noticed muscle weakness in her lower extremities. She stopped sniffing thinner because she had a mild fever on July 1 and 2, but from July 3 through 5 she sniffed about five times each day (Fig. 1). She had consumed approximately 6 1 of thinner during the month prior to her second admission on July 6 for severe vertigo and muscle weakness. The patient was otherwise alert and well oriented. Physical examination was negative, except for muscle weakness. The laboratory studies showed mixed hyperchloremic and high anion gap metabolic acidosis (Table 1). Urine examination revealed proteinuria, myoglobinuria, and glucosuria. The concentration of serum aldosterone was above normal. After treatment, she regained muscle strength and electrolyte balance. Urinary findings normalized. She came to the hospital again on August 18, which was 19 d after discharge, at which time her breath smelled strongly of thinner. Arterial blood gas analysis revealed high anion gap metabolic acidosis, and the urinary hippuric acid level was 22.7 g/l at that time.


Special studies

Excretion rate of phenolsulfonphthalein (July 16). The patient drank 500 ml of water, and after 30 min, 1 ml (6 mg) of phenolsulfonphthalein was injected intravenously. Urine was collected at intervals of 15, 30, and 60 min; the percentage of dye excreted was 19.2 (normal value: 25-50), 36.6 (40-60), and 52.9 (50-75), respectively.

Fishberg concentration test (July 24). The patient was asked to urinate prior to retiring to bed. After a 12-h fast, the urine specimens were collected at 6, 7, and 8 o'clock the next morning. Urinary specific gravity was measured, and the values were 1.016, 1.018, and 1.020, respectively (normal value: > 1.022 in any specimen).

Renal biopsy (July 24). Light microscopy of the biopsy specimen revealed patchy areas of tubular injury with cellular casts. Glomeruli and vessels were almost normal (Fig. 2). Immunofluorescence staining revealed normal findings.

Excretion rate of bicarbonate (July 29). The patient was given 5.0 g of sodium bicarbonate orally on July 28 and 29. Concentration of creatinine and bicarbonate in the serum and urine were determined. The excretion rate of bicarbonate was calculated to be 2.9% (normal value: < 3%).

Short ammonium chloride loading test (July 30). The patient was given 5.0 g of ammonium chloride orally, after which urine was collected at 1-h intervals until the pH was < 5.3 (normal value: < 5.3). Three urine collections were made. The lowest urinary pH noted was 5.18.


The patient had no history of renal disease, except when she was 19. Any potential nephrotoxic agents, other than toluene, did not exist. We, therefore, concluded that the exposure to extremely high doses of pure toluene induced mixed hyperchloremic and high anion gap metabolic acidosis in our patient. The acidosis seemed to be distal renal tubular acidosis (distal RTA) because of an abnormally high urine pH for acidemia. The laboratory data also indicated both proximal and distal tubular damage, which accords with the results cited in two reported cases.[5,9] The diagnosis, however, was not confirmed completely. We failed to measure the excretion rate of NH[4], which was necessary to diagnose RTA.[3]

There have been some reports on histological changes in the kidneys of toluene sniffers.[7,11-17] We classified the reported cases into three groups: (1) glomerular lesions, (2) tubular lesions, and (3) almost normal Table 2). In the reports of the glomerular lesion group, arterial pH was not mentioned. The reports did not include mention of any relationship between thinner sniffing and metabolic acidosis, and they failed to clarify the nephrotoxicity of toluene, although mesangiocapillary glomerulonephritis in the cases might have been related to solvent exposure, as suspected in workers.[18,19]


Organic anions, such as p-aminohippurate, hippuran, phenolsulfonphthalein, and hippuric acid, are transported from the blood into the proximal tubular cells and excreted into the tubular lumen by the organic anion transport system.[20] It was plausible that hippuric acid was accumulated within the cells and injured them. We attributed the degeneration of renal tubules to myoglobinuria and to the direct effect of toluene metabolites. Nontraumatic rhabdomyolysis accompanied by myoglobinuria is a relatively common cause of acute renal failure.21 Acute renal failure has sometimes occurred in thinner-sniffers and has been accompanied by an elevation of serum creatinine kinase CK) or myoglobin. [11,15,22,23] Streicher et al. suggested that toluene might have been primarily toxic to the muscle membranes.[17]

The half-life of toluene in the blood was 21 h,[24] and blood toluene almost disappeared within 150 h after an exposure to a high dose of solvent that contained toluene.[9,24] In our patient, dysfunction and morphological changes of renal tubules remained after acidosis normalized on the fourth day of admission. The hippuric acid level in urine was extremely high and implied excessive production of benzoic acid and hippuric acid in the blood. Microscopic findings, therefore, provide support for the notion that toluene is a tubular toxin and may contribute to the development of distal RTA.

Much remains to be elucidated regarding the mechanism of metabolic acidosis associated with toluene. Further studies on nephrotoxicity of aromatic hydrocarbons are necessary, as well as the investigation of a doseeffect relationship between toluene exposure and acidosis.

Submitted for publication June 8, 1993; revised; accepted for publication September 27, 1993.

Requests for reprints should be sent to: Michihiro Kamijima, M.D., Department of Hygiene, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466, Japan.


[1.] Taher S, Anderson R, McCartney R, et al. Renal tubular acidosis associated with toluene "sniffing." N Engl J Med 1974; 290:765-68. [2.] Fischman C, Oster J. Toxic effects of toluene: a new cause of high anion gap metabolic acidosis. J Am Med Assoc 1979; 241:1713-15. [3.] Carlisle E, Donnelly S, Vasuvattakul S, et al. Glue-sniffing and distal renal tubular acidosis: sticking to the facts. J Am Soc Nephrof 1991; 1:1019-27. [4.] Vasuvattakul S, Nimmannit S, Shayakul C, et al. Should the urine [PCO.sub.2] or the rate of excretion of ammonium be the gold standard to diagnose distal renal tubular acidosis? Am J Kid Dis 1992; 19:72-75. [5.] Moss A, Gabow P, Kaehny W, et al. Fanconi's syndrome and distal renal tubular acidosis after glue sniffing. Ann intern Med 1980; 92:69-70. [6.] Bennett R, Forman H. Hypokalemic periodic paralysis in chronic toluene exposure. Arch Neurol 1980; 37:673. [7.] Kroeger M, Moore R, Lehman T, t al. Recurrent urinary calculi associated with toluene sniffing. J Urol 1980; 123:89-91. [8.] Suhara T, Shimizu T, Sunada Y, et al. A case of distal renal tubular acidosis associated with toluene sniffing. Nippon Naika Gakkai Zasshi 1988; 77:1452-53 (in Japanese). [9.] Batlle D, Sabatini S, Kurtzman N. On the mechanism of toluene-induced renal tubular acidosis. Nephron 1988; 49:210-18. [10.] Nakamoto M, Uehara H, Nishihira T, et al. Distal renal tubular acidosis associated with toluene sniffing. Chudoku Kenkyu 1989; 2:411-13 (in Japanese). [11.] Mizutani T, Ohashi N, Naito H. Myoglobinemia and renal failure in toluene poisoning: a case report. Vet Human Toxicol 1989; 31:448-50. [12.] Venkataraman G. Renal damage and glue sniffing. Br Med J 1981; 283:1467. [13.] Hamilton D, Thiru S, Evans D. Renal damage and glue sniffing. Br Med J 1982; 284:117. [14.] Russ G, Clarkson A, Woodroffe A, et al. Renal failure from "glue sniffing" Med J Aust 1981; 2:121-22. [15.] Ando Y, Tabei K, Kato K, et al. A case of "glue-sniffing" with acute tubular necrosis due to rhabdomyolysis. Jin To Toseki 1987; 22:317-22. [16.] Taverner D, Harrison D, Bel.1 G. Acute renal failure due to interstitial nephritis induced by glue-sniffing with subsequent recovery. Scot Med J 1988; 33:246-47. [17.] Streicher H, Gabow P, Moss A, et al. Syndromes of toluene sniffing in adults. Ann intern Med 1981; 94:758-62. [18.] Steenland K, Thun M, Ferguson W, et al. Occupational and other exposures associated with male end-stage renal disease. A case/control study. Am j Public Health 1990; 80:153-57. [19.] Porro A, Lomonte C, Coratelli P, et al. Chronic glomerulonephritis and exposure to solvents: a case-referent study. Br J ind Med 1992; 49:738-42. [20.] Burckhart G, Ullrich K. Organic anion transport across the contraluminal membrane-dependence on sodium. Kidney int 1989; 36:370-77. [21.] Grossman R, Hamilton R, Morse B, et al. Nontraumatic rhabdomyolysis and acute renal failure. N Engi J Med 1974; 291:807-11. [22.] Reisin E, Teicher A, jaffe R, et al. Myoglobinuria and renal failure in toluene poisoning. Br J Ind Med 1975; 32:163-64. [23.] Gupta R, van der Meulen J, Johny K. Oliguric acute renal failure due to glue-sniffing. Scand J Urol Nephrol 1991; 25:247-50. [24.] Brugnone F, Perbellini L, Apostoli P, et al. Decline of blood and alveolar toluene concentration following two accidental human poisonings. Int Arch Occup Environ health 1983; 53:157-65.

COPYRIGHT 1994 Heldref Publications
COPYRIGHT 2004 Gale Group

Return to Metabolic acidosis
Home Contact Resources Exchange Links ebay