TUBULAR DISEASE:

Renal tubular acidosis:

RTAs comprise disorders affecting either PCT or DCT. They are characterized by hyperchloremic, normal anion gap; metabolic acidosis. They are the result of either failure to retain bicarbonate or inability of renal tubules to secrete hydrogen ions.

The three categories of RTA are distal (dRTA, type I); proximal (pRTA, type II); and type IV, which is secondary to aldosterone deficiency or resistance. The term type III RTA (mixed proximal/distal defect) is not used.

Distal RTA (Type I): 

Clinical feature includes metabolic acidosis, muscle weakness, urolithiasis, nephrocalcinosis. The defect is an inability to secrete hydrogen ions in the distal tubule in the presence of systemic acidosis. Urinary pH >5.5 is a common feature. Due to inability to secrete hydrogen, Na reabsorption occurs by exchanging K in distal tubule and there is increased renal potassium loss producing hypokalaemia. The defect may be in H⁺-ATPase or H⁺, K⁺-ATPase transporter.

Proximal RTA (Type II): 

Here the primary defect is failure of proximal tubular bicarbonate reabsorption. Here the threshold of bicarbonate reclamation is lowered to 15 mmol/L from 22 mmol/L. The filtered load of bicarbonate when falls to a point at which hydrogen ion secretion is sufficient to reabsorb all filtered bicarbonate, then only bicarbonate is reclaimed. The plasma bicarbonate decreases to 15-20 mmol/L. Here the urinary pH will be <5.5 as the bicarbonate will be reclaimed after this threshold has reached.

Selective aldosterone deficiency (type IV RTA): 

There is failure of distal potassium and hydrogen ion secretion due to aldosterone deficiency or resistance. There is hyporeninemic hypoaldosteronism. Hyperkalemia is usual manifestation and failure to reabsorb sodium in exchange of chloride will produce hyperchloremia. There is also defective ammonia formation and may be due to glutaminase deficieny or defect.

Diagnosis of RTA:

The finding of early morning urinary pH <5.5 in presence of systemic acidosis supports the diagnosis of pRTA, since distal function is well. In dRTA the urinary pH is >5.5, hypophosphataemia.

The plasma potassium can give the clue (high in Type IV and low in Type I and II). In type IV there is also urine pH >5.5 but there is hyperkalaemia.

Fractional bicarbonate excretion can confirm diagnosis of pRTA as long as the patient’s plasma bicarbonate is maintained above 20 mmol/L

(Urine bicarbonate/plasma bicarbonate)/(urine creatinine/plasma creatinine) x 100%

In pRTA this is >10-15%, whereas in most cases of dRTA it is <10%.

Generalized tubular defects (Fanconi syndrome):

During this there is generalized renal tubular defect. There is a failure in net proximal tubular reabsorption of glucose, amino acids, phosphate and bicarbonate with consequent glycosuria, amino aciduria, phsophaturia and acidosis together with vitamin D-resistant metabolic bone disease. Although the exact mechanism is unknown; the cause may be inherited defect like cystinosis, fructose intolerance, galactosemia, glycogen storage disease type I and acquired like heavy metal poisoning, drugs (tetracycline, gentamicin), paraproteinaemia, amyloidosis. The clinical features are polyuria, polydipsia, dehydration, hypokalemia and acidosis, with impaired growth and rickets in children and osteomalacia in adults.