Retinal acidosis

Cobalamin-c disease remethylation of homocysteine to methionine also requires an activated form of vitamin B12. In the absence of normal B12 activation, homocystinuria results from a failure of normal vitamin B12 metabolism. Complementation analysis classifies defects in vitamin B12 metabolism into three groups cblC (most common), cblD and cblF. Most individuals become ill in the first few months or weeks of life with hypotonia, lethargy and growth failure. Optic atrophy and retinal changes can occur. Methylmalonate excretion is excessive, but less than in methylmalonyl-CoA mutase deficiency, and without ketoaciduria or metabolic acidosis. 

A serious toxicity of didanosine is pancreatitis, which may be fatal (see Warnings). Other important toxicities include lactic acidosis/severe hepatomegaly with steatosis retinal changes and optic neuritis and peripheral neuropathy (see Warnings and Precautions). 

Methanol is metabolized to formaldehyde and formic acid, which injure the retinal cells and optic nerves, and lead to severe acidosis. Treatment delay increases morbidity. Thus, early recognition and management are crucial. Clinical features emerge up to 36 hours after ingestion. Nausea, vomiting, abdominal pain, headache, dizziness, paraesthesia, blurred vision, and diminished visual activity may occur, and coma supervenes. Dilated, unreactive, pupils predict permanent blindness. 

MELAS, Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes CPEO, chronic progressive external ophthalmoplegia LHON, Leber hereditary optic neuropathy NARP, neurogenic muscle weakness, ataxia, and retinitis pigmentosa NIDDM, non-insulin-dependent diabetes mellitus TER, termination. 

Intoxication may present as inebriation and drowsiness similar to ethanol use. Other symptoms are vomiting, diarrhea, delirium and agitation, back and abdominal pain, and clammy skin. Toxic effects usually follow a latent period of several hours. Formate inhibits mitochondrial cytochromes resulting in neurotoxicity. Ocular signs include blurred vision, dilated pupils, and direct retinal toxicity with optic disc hyperemia and ultimately permanent blindness [91]. Cerebral hemorrhagic necrosis has been reported [92]. Severe poisoning may result in Kussmaul respiration, inspiratory apnea, coma, and death. Urine samples may have the characteristic smell of formaldehyde. An elevated serum osmolal gap from methanol will be evident early in presentation but may disappear after approximately 12 hours. At this time, an elevated anion gap metabolic acidosis from retained formate may be evident. 

Major toxic effects are caused by formaldehyde and formic acid. The former is responsible for damage to retinal cells that may cause blindness, while the latter produces severe acidosis that may eventually lead to death. A minor effect of methanol is depression of the central nervous system (CNS). Retardation of the first step in the oxidation of methanol is accomplished by administration of ethanol, the oxidation products of which are not as toxic as those of methanol. Other therapeutic modalities include removal of methanol by gastric lavage (to prevent further absorption), hemodialysis (to remove absorbed methanol), and administration of exogenous bicarbonate (for treatment of severe acidosis). 

Methanol, which has caused many fatalities when ingested accidentally or consumed as a substitute for beverage ethanol, is metabolically oxidized to formaldehyde and formic acid. In addition to causing acidosis, these products affect the central nervous system and the optic nerve. Acute exposure to a lethal dose causes an initially mild inebriation, followed in about 10-20 hours by unconsciousness, cardiac depression, and death, Subletal exposures can cause blindness from deterioration of the optic nerve and retinal ganglion cells. Inhalation of methanol fumes may result in chronic, low level exposure. 

A. Methanol Methanol (wood alcohol) is sometimes used by alcoholics when they are unable to obtain ethanol and is a constituent of windshield cleaners and canned heat Intoxication from methanol alone may include visual dysfunction, gastrointestinal distress, shortness of breath, loss of consciousness, and coma. Methanol is metabolized to formaldehyde and formic acid, which can cause severe acidosis, retinal damage, and blindness. The formation of formaldehyde is retarded by prompt intravenous administration of ethanol, which acts as a preferred substrate for alcohol dehydrogenase and competitively inhibits the oxidation of methanol (Figure 23-2). 

Carbon monoxide Coma, metabolic acidosis, retinal hemorrhages... 

This phenomenon was first observed in a case of diabetic acidosis by Heyl (1880) and quite certainly only reflects the degree of plasma turbidity resulting from increase in VLDLP and/or chylomicrons. The fundus in lipemia retinalis is characteristic and can only be imitated to some degree by leukemias. The retinal vessels appear flattened and show increased light reflexes arteries and veins are difficult to distinguish on a salmon colored background. Vision is usually not impaired, and the case of de Rosa (1952) with blindness of the left eye was due to other changes (atrophy of the left optic nerve with massive lipid deposits lateral to the optic disc.)... 

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