Renal acidosis

The renal lesions which have been described in idiopathic hypercalcemia are not specific. Similar changes have been observed in hyperchloremic renal acidosis of infancy (B7, D7), in various other diseases of infancy and in hypervitaminosis D. It is interesting to note that a recent re-examination of the histological sections of Thatcher s cases of a quarter of a century ago showed that the changes there were essentially the same as those occurring in idiopathic hypercalcemia of infancy (Rl). 

D7. Doxiadis, S. A., Idiopathic renal acidosis in infancy. Arch. Disease Childhood 27, 409-427 (1952). 

As described above, high therapeutic doses of salicylate are associated with a primary respiratory alkalosis and compensatory renal acidosis. Subsequent changes in acid—base status generally occur only when toxic doses of salicylates are ingested by infants and children or occasioncdly after large doses in adults. 

The phase of primary respiratory alkalosis rarely is recognized in children with salicylate toxicity. They usually present in a state of mixed respiratory and renal acidosis, characterized by a decrease in blood pH, a low plasma bicarbonate concentration, and normal or nearly normal plasma PCO2. Direct salicylate-induced depression of respiration prevents adequate respiratory hyperventilation to match the increased peripheral production of CO2- Consequently, plasma PCO2 increases and blood pH decreases. Because the concentration of bicarbonate in plasma already is low due to increased renal bicarbonate excretion, the acid-base status at this stage essentially is an uncompensated respiratory acidosis. Superimposed, however, is a true metabolic acidosis caused by accumulation of acids as a result of three processes. First, toxic concentrations of salicylates displace 2-3 mEq/L of plasma bicarbonate. Second, vasomotor depression caused by toxic doses of salicylates impairs renal function, with consequent accumulation of sulfuric and phosphoric acids. Third, salicylates in toxic doses may decrease aerobic metabolism as a result of inhibition of various enzymes. This derangement of carbohydrate metabolism leads to the accumulation of organic acids, especially pyruvic, lactic, and acetoacetic acids. 

Maschio G, Bazzato G, Bertaglia E, Sardini D Mioni G. (1970). Intracellular pH and electrolyte content of skeletal muscle in patients with chronic renal acidosis. Nephron 7,481 87. 

These observations on the effect of body fluid volumes and electrolyte concentrations on aldosterone secretion may have some bearing on the pathogenesis of classical clinical changes. For example, in renal tubular acidosis there is an obligatory sodium loss. The plasma potassium levels are decreased, and aldosterone secretion is stimulated. The administration of bicarbonate, a procedure which usually leads to potassium diuresis, induces potassium retention in these cases. To explain such intricate interactions between hormonal secretion, body fluid volume, and ion concentration, one could assume that the sodium loss, which is obligatory in renal acidosis, leads to reduction in the body fluid volume followed by a loss of potassium. The administration of bicarbonate, which prevents sodium loss and thereby influences the body fluid volume, reduces aldosterone secretion and prevents the loss of potassium ions. 

Patients with primary proximal tubular acidosis usually have stable serum HCO3 levels in spite of the reduced acid excretion. The compensatory mechanism is not known, but reduced endogenous acid production can probably be excluded. A more likely adaptation is the formation of additional bases at the expense of bone CaC03. Some patients with primary proximal acidosis present skeletal demineralization, reduced levels of CO3 in the hydroxyapatite crystals, and increased calcium losses in the feces. Patients with proximal renal acidosis are usually symptomless, and except in cases of acid overproduction, the prognosis is usually favorable. 

In nephropathic cystinosis clinical chemistry of blood and urine reveals Fanconi syndrome with glucosuria, generalized hyperaminoaciduria and hyperphosphaturia. Most patients show polyuria and loose potassium and bicarbonate resulting in hypokalemia and renal acidosis. Additional tubular losses of calcium, magnesium and carnitine might also occur. The degree of tubular dysfunction is variable in any patient, but also dependent upon... 

Clinical assessment of pulmonary status is based on history, auscultation and noninvasive pulse oximetry/arterial blood gas analysis on room air. Chest radiography and spirometry are indicated only in patients with known or suspected significant pulmonary disease. Chronic pleural effusion may require preoperative drainage to support respiratory compensation of renal acidosis, the more so if sedation is planned. Current medication regimens should be optimized. 

Clinically, the signs and symptoms vary with the degree of hypoplasia and the underlying cause or associated disease. Many children are otherwise healthy, and renal hypoplasia is detected by chance others with a more severe disease state may suffer from urinary tract infection, hypertension-pre-dominantly in Ask-Upmark kidney, renal acidosis or signs of chronic renal failure. 

Metformin Renal or liver disease any predisposition to hypoxia Gastro intestinal upsets risk of lactic acidosis if wrongly prescribed Creatinine, Hb or Vit B12b... 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Metformin is contraindicated in patients with heart failure, renal disease, hypersensitivity to metformin, and acute or chronic metabolic acidosis, including ketoacidosis. The drug is also contraindicated in patients older than 80 years and during pregnancy (Pregnancy Category B) and lactation. 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

This electrolyte plays a vital role in the acid-base balance of the body. Bicarbonate may be given IV as sodium bicarbonate (NaHC03) in the treatment of metabolic acidosis, a state of imbalance that may be seen in diseases or situations such as severe shock, diabetic acidosis, severe diarrhea, extracorporeal circulation of blood, severe renal disease, and cardiac arrest. Oral sodium bicarbonate is used as a gastric and urinary alkalinizer. It may be used as a single drug or may be found as one of the ingredients in some antacid preparations. It is also useful in treating severe diarrhea accompanied by bicarbonate loss. 

Potassium is contraindicated in patients who are at risk for experiencing hyperkalemia, such as those with renal failure, oliguria, or azotemia (file presence of nitrogen-containing compounds in the blood), anuria, severe hemolytic reactions, untreated Addison s disease (see Chap. 50), acute dehydration, heat cramps, and any form of hyperkalemia Potassium is used cautiously in patients with renal impairment or adrenal insufficiency, heart disease, metabolic acidosis, or prolonged or severe diarrhea. Concurrent use of potassium with... 

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

Excretion into urine of ammonia produced by renal mbu-lar cells facilitates cation conservation and regulation of acid-base balance. Ammonia production from intracellular renal amino acids, especially glutamine, increases in metabolic acidosis and decreases in metabolic alkalosis. 

Osteopetrosis (marble bone disease), characterized by increased bone density, is due to inability to resorb bone. One form occurs along with renal tubular acidosis and cerebral calcification. It is due to mutations in the gene (located on chromosome 8q22) encoding carbonic anhydrase II (CAII), one of four isozymes of carbonic anhydrase present in human tissues. The reaction catalyzed by carbonic anhydrase is shown below ... 

Phenylephrine 10-1000 pg/minute Seconds Bradycardia, coronary vasoconstriction, decreased renal perfusion, metabolic acidosis Alpha-1, increased cardiac output (CO), decreased systemic vascular resistance (SVR)... 

Stimulation of basolateral Na /H exchanger transport activity in LLC-PK] cells during chronic metabolic acidosis is accompanied by a parallel increase in NHE-1 transcript abundance [80]. Chronic metabolic acidosis also increases the abundance of Na /H exchanger transcripts in rat renal cortices [81] and SV40-transformed mouse proximal tubule cells [82]. 

Chronic or large ingestions of propylene glycol have been associated with the development of hyperosmolar anion-gap metabolic acidosis, renal dysfunction, hemolysis, cardiac arrhythmias, and seizures. 

Poorly treated hyperthermia may lead to metabolic acidosis, rhabdomyolysis, elevated aminotransferases, seizures, renal failure, and disseminated intravascular coagulation (DIC)... 

Renal losses (e.g., proximal [Type II] renal tubular acidosis [RTA])... 

The dose of adefovir dipivoxil is 10 mg once daily. The most common side effects include asthenia, abdominal pain, diarrhea, dyspepsia, headaches, nausea, and flatulence. Lactic acidosis, pancreatitis, and hepatomegaly have been reported rarely. Unlike lamivudine, adefovir dipivoxil is associated with dose-related nephrotoxicity, which was most commonly seen in HIV patients receiving doses larger than 60 mg. Therefore, the dose of adefovir dipivoxil must be adjusted in patients with renal insufficiency (CrCl less than 50 mL/minute). 

The side-effect profile for entecavir is similar to lamivudine and adefovir dipivoxil and comparable to placebo. Patients treated with entecavir should be monitored for signs and symptoms associated with lactic acidosis and severe hepatomegaly with steatosis, because some cases have been fatal. Dosage adjustments are required in patients with renal dysfunction. 

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