Severe acidosis

Solutions of weak acids or bases and their conjugates exhibit buffering, the abihty to resist a change in pH following addition of strong acid or base. Since many metabohc reactions are accompanied by the release or uptake of protons, most intracellular reactions are buffered. Oxidative metabohsm produces CO2, the anhydride of carbonic acid, which if not buffered would produce severe acidosis. Maintenance of a constant pH involves buffering by phosphate, bicarbonate, and proteins, which accept or release protons to resist a change... 

During phase I, each seizure causes a sharp increase in autonomic activity with increases in epinephrine, norepinephrine, and steroid plasma concentrations, resulting in hypertension, tachycardia, hyperglycemia, hyperthermia, sweating, and salivation. Cerebral blood flow is also increased to preserve the oxygen supply to the brain during this period of high metabolic demand. Increases in sympathetic and parasympathetic stimulation with muscle hypoxia can lead to ventricular arrhythmias, severe acidosis, and rhabdomyolysis. These, in turn, could lead to hypotension, shock, hyperkalemia, and acute tubular necrosis. 

Disorders of glutathione Defective synthesis of glutathione, the major intracellular antioxidant Spinocerebellar degeneration, mental retardation, cataracts, hemolysis. Severe acidosis in some cases N-acetylcysteine (variable response)... 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Noninvasive positive-pressure ventilation (NPPV) provides ventilatory support with oxygen and pressurized airflow using a face or nasal mask with a tight seal but without endotracheal intubation. In patients with acute respiratory failure due to COPD exacerbations, NPPV was associated with lower mortality, lower intubation rates, shorter hospital stays, and greater improvements in serum pH in 1 hour compared with usual care. Use of NPPV reduces the complications that often arise with invasive mechanical ventilation. NPPV is not appropriate for patients with altered mental status, severe acidosis, respiratory arrest, or cardiovascular instability. 

In those patients who survive more than a few weeks, the effects of renal tubular dysfunction become more severe. Acidosis and hypo-phosphatemic rickets are prominent features. The urine is alkaline and gives a strong Rothera reaction. However, the ability to concentrate the urine is never lost and there is neither polydipsia nor polyuria. Aminoaciduria, hydroxyphenyluria, glucosuria, fructosuria, and proteinuria continue. The liver remains large and cirrhotic. Death finally occurs in liver failure, sometimes after several years. There is evidence that some children recover with no residual signs other than a large firm liver. 

Bennett IL, Janies D, Golden A. 1950. Severe acidosis due to phenol poisoning Report of two cases. Ann Intern Med 32 324-327. 

The peptide hormone insulin (see Box 13.1) is produced by the pancreas and plays a key role in the regulation of carbohydrate, fat, and protein metabolism, hi particular, it has a hypoglycaemic effect, lowering the levels of glucose in the blood. A malfunctioning pancreas may produce a deficiency in insulin synthesis or secretion, leading to the condition known as diabetes mellitus. This results in increased amounts of glucose in the blood and urine, diuresis, depletion of carbohydrate stores, and subsequent breakdown of fat and protein. Incomplete breakdown of fat leads to the accumulation of ketones in the blood, severe acidosis, coma, and death. 

The LDso values for picric acid after oral dosing of male and female rats were 290 and 200 mg/kg, respectively. Death was due to severe acidosis, with toxic doses of picric acid exceeding the buffering capacity of the blood. In rats, metabolism of picric acid is primarily limited to reduction of nitro groups of the aromatic ring and subsequent conjugation by acetate. 

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. 

Ethylene glycol Poisoning creates toxic aldehydes and oxalate, which causes kidney damage and severe acidosis ... 

Ition of the ketone bodies may be as high as 5000 mg/24 hr, and the blood concentration may reach 90 mg/dl (versus less than 3 mg/dL in normal individuals). A frequent symptom of diabetic ketoacidosis is a fruity odor on the breath which result from increased production of acetone. An elevation of the ketone body concentration in the blood results in acidemia. [Note The carboxyl group of a ketone body has a pKa about 4. Therefore, each ketone body loses a proton (H+) as it circulates in the blood, which lowers the pH of the body. Also, excretion of glucose and ketone bodies in the urine results in dehydration of the body. Therefore, the increased number of H+, circulating in a decreased volume of plasma, can cause severe acidosis (ketoacidosis)]. Ketoacidosis may also be seen in cases of fasting (see p. 327). 

Iron poisoning is characterized by vomiting, abdominal pain, gastroenteritis, and shock, and if not properly treated, severe acidosis, coma, and death ensue. Deferoxamine, which binds iron, is used as the preferred chelator in treating iron poisoning. The metabolic acidosis may be appropriately... 

On the other hand, drugs may inhibit the metabolism of other drugs. For example, allopurinol (a xanthine oxidase inhibitor that inhibits the synthesis of uric acid) increases the effectiveness of anticoagulants by inhibiting their metabolism. Chloramphenicol (a potent inhibitor of microsomal protein synthesis) and cimetidine (an H2-receptor blocker used in acid-pepsin disease) have similar properties. In addition, drugs may compete with each other in metabolic reactions. In methyl alcohol (methanol) poisoning, ethyl alcohol may be given intravenously to avert methanol-induced blindness and minimize the severe acidosis. Ethyl alcohol competes with methyl alcohol for... 

The signs and symptoms of diabetes consist of thirst, anorexia, nausea, vomiting, abdominal pain, headache, drowsiness, weakness, coma, severe acidosis, air hunger (Kussmaul s breathing), sweetish odor of the breath, hyperglycemia, decreased blood bicarbonate level, decreased blood pH, and plasma that is strongly positive for ketone bodies. 

The pH of normal urine can vary between 4.7 through 8.0. The usual value is about 6.0. High-protein diets and fever can lower the pH of urine. In severe acidosis, the pH may be as low as 4.0. Vomiting and respiratory or metabolic alkalosis can raise the pH above 8.0. 

A child with biotinidase deficiency should be adequately hydrated to facilitate the excretion of the abnormal organic acid metabolites (Fig. 12-2). Adequate nutrition is essential. In the acute stage of the disorder, protein may be restricted. It is imperative to supply sufficient calories in the form of parenteral glucose or oral polysaccharides, such as polycose. Severe acidosis may initially require bicarbonate supplementation. 

Bicarbonate Current guidelines state that acidosis need not be corrected using exogenous bicarbonate therapy. Intravenous administration of fluids and insulin are sufficient to correct the metabolic acidosis and to regenerate bicarbonate. Some practitioners believe, however, that bicarbonate repletion should be provided in the setting of severe acidosis with pH less than 6.9. 

Glutathione synthetase (GSS), in mammalian cells, is a homodimer of 52-kD protein. In humans, the GSS gene contains 13 exons (encoding 474 amino acids) on chromosome 20qll.2. There are rare cases of inherited GSS deficiency as a result of missense mutations and splice mutations. GSS deficiency patients have severe acidosis and hemolytic anemia. 

Cocaine-induced delirium with severe acidosis has been reported (175). 

Allam S, Noble JS. Cocaine-excited delirium and severe acidosis. Anaesthesia 2001 56(4) 385-6. 

Toxicity. The minimum lethal dose has been estimated as 25 ml orally and 12 ml rectally, although recovery has occurred after the ingestion of 125 ml. Toxic effects have been associated with blood concentrations of 200 to 400 pg/ml. Blood concentrations of about 500 pg/ml, or less if alcohol has also been ingested, may be lethal. On storage, paraldehyde may depolymerise to acetaldehyde and acetic acid severe acidosis and fatalities may follow the use of partly depolymerised material. 

CAIs alter renal function primarily by inhibiting carbonic anhydrase in the proximal tubule, which results in decreased bicarbonate reabsorption. The net effect of the renal actions of acetazolamide therapy is alkaliniza-tion of the urine and metabolic acidosis. Metabolic acidosis results from the initial bicarbonate loss and persists with continued acetazolamide use. Moderate metabolic acidosis develops in most patients. Reabsorption of bicarbonate independent of carbonic anhydrase prevents severe acidosis. Initially, acetazolamide produces diuresis, but urinary output decreases with the development of metabolic acidosis. In addition, decreased urinary citrate excretion follows acetazolamide therapy and has been attributed to the metabolic acidosis it produces. A high urinary pH and low urinary citrate concentration are conducive to precipitation of calcium phosphate in both the renal papillae and the urinary tract. 

Certain pathological conditions can lead to a life-threatening rise in the blood levels of the ketone bodies. Most common of these conditions is diabetic ketosis in patients with insulin-dependent diabetes mellitus. The absence of insulin has two major biochemical consequences. First, the liver cannot absorb glucose and consequently cannot provide oxaloacetate to process fatty acid-derived acetyl CoA (Section 17.3.1). Second, insulin normally curtails fatty acid mobilization by adipose tissue. The liver thus produces large amounts of ketone bodies, which are moderately strong acids. The result is severe acidosis. The decrease in pH impairs tissue function, most importantly in the central nervous system. 

Clinical evidence suggestive of analgesic nephropathy includes nocturia, renal insufficiency with severe acidosis, persistent urinary tract infection with colic, hematuria, and hypertension (40,41). Nocturia resulting from failure to concentrate urine is usually the earliest functional defect, but like the other symptoms it is non-specific, rendering the diagnosis of analgesic nephropathy difficult. A CT scan showing bilateral small kidneys with bumpy contours, and papillary calcification is accepted to be of sufficient specificity (38,39). 

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