Can occur in a variety of diseases and is a clinical manifestation; acidosis due to impaired hydrogen secretion in the distal tubule and impaired HCO3- reabsorption in the proximal tubule; generally normal anion gap, hyperchloremic metabolic acidosis; divided into 4 types, type I and IV being the most common; distal tubular acidosis (type I) Pathogenesis: failure to establish luminal and peritubular H+ gradients – impaired hydrogen secretion, impaired proton pump, decreased luminal negative potential Clinical manifestations: imbalance of acid-base balance – hyperchloremic metabolic acidosis, decreased urinary titratable acid, urinary pH > 5.5 (urinary pH depends mainly on titratable acid); electrolyte disturbances: hypokalemia, decreased renal reabsorption of calcium due to acidosis leading to low blood calcium, high urinary calcium; secondary hyperparathyroidism leading to low blood phosphorus, high urinary phosphorus; bone disease, renal calculi, renal calcification; diagnosis: general criteria: hyperchloremic acidosis urinary titratable acid and NH4+ reduction, pH > 6, low potassium; ammonium chloride loading test Input of ammonium chloride makes patient acidotic, normal urinary pH < 5.5, dRTA urinary pH > 5.5 urinary PCO2 determination Normal: U-B PCO2 > 20 mmHg difference between urine and blood RTA: U-B PCO2 < 20 mmHg less H in urine cannot neutralize HCO3 to produce CO2 Treatment: Alkaline drug supplementation 1-2meq/kg/d, potassium supplementation, calcium or VD3 available for bone disease (beware of kidney stones) Proximal tubular acidosis (type II) Pathogenesis: HCO3-absorption disorders - Na-H exchange abnormalities, Na-HCO3 isotransport abnormalities on one side of the tissue gap, CA abnormalities, often accompanied by complex proximal tubular function defects, resulting in Fanconi syndrome (glucose, amino acids, phosphate, uric acid, etc.). (abnormal absorption of glucose, amino acids, phosphate, uric acid, etc.) Clinical manifestations: imbalance of acid-base balance - hyperchloremic acidosis, more HCO3- in urine, normal titratable acid and NH4+, urinary pH <5.5; imbalance of electrolyte balance - hypokalemia is obvious (less Na absorption in proximal tubules, more Na-K exchange in distal tubules, similar to the effect of carbonic anhydrase inhibitors). Hypocalcemia and hypophosphatemia are mild; bone disease is mild, renal stone and renal calcification are rare; also associated with Fanconi syndrome; diagnosis: hyperchloremic acidosis, more HCO3- in urine, urinary PH <5.5, hypokalemia; bicarbonate filtration excretion fraction: normal value is 0, pRTA>15% pRTA treatment: correction of acidosis, appropriate application of thiazide diuretics: reduce hemolysis, enhance the absorption of HCO3 Hypokalemia Correction of hypokalemia Mixed tubular acidosis (type III) Type I + type II – decrease in titratable acid and NH4+ in urine with increase in HCO3-; hyperkalemic tubular acidosis (type IV) Mostly seen in the elderly with renal insufficiency; hyperchloremic acidosis and hyperkalemia are the main manifestations; may be related to reduced secretion of aldosterone or diminished response; Fanconi syndrome Proximal tubular complex Dysfunction, impaired reabsorption of a variety of substances renal glycosuria, amino aciduria, hyperuricuria, phosphaturia, uric aciduria; often accompanied by type 2 renal tubular acidosis (low potassium, low phosphorus, low calcium) Treatment principles of RTA Treatment of the primary disease: the condition of the primary disease is controlled in time, the patient’s symptoms can be significantly improved. Alkaline drugs: such as sodium bicarbonate or sodium citrate supplementation Mineral supplementation: if hypokalemia, hypomagnesemia or hypophosphatemia exist, the corresponding electrolytes should be supplemented, and timely symptomatic treatment should be given. Diuretics: For type IV RTA, tachyphylaxis or butanuric acid or dihydrocortisone can be given to increase potassium excretion and correct hyperkalemia. Salt corticosteroids: For patients with type IV RTA, oral adrenocorticosteroids can be given to increase the excretion of H+ and K+. Control complications of RTA: such as stones, infections, etc. I II III IV Serum chloride elevated elevated elevated elevated plasma HCO3 lowered lowered lowered plasma pH lowered lowered lowered lowered blood potassium lowered lowered elevated urinary pH >5.5 <5.5 >5.5 <5.5 FEHCO3 <15 % >15 % <15 % <15 % U-BPCO2(mmHg) <20 >20 <20 20 <20 <20 Urinary NH4+ Decreased Normal Decreased Decreased Other Kidney stones, bone disease Secondary hyperparathyroidism Fanconi syndrome Kidney stones Aldosterone decreased