Monday, December 20, 2010
9:19 AM | Posted by Shams Burki | Edit Post
Clinical Vignette: A 24-year-old man with progressive low back pain and weakness ﬁnally sees his doctor on account of an episode of left loin pain. Investigations show haematuria and a urinary pH of 7.
Other investigations show:
Other investigations show:
- Plasma sodium 135 mmol/L
- Plasma potassium 2.8 mmol/L
- Plasma urea 5.7 mmol/L
- Plasma creatinine 107 μmol/L
- Plasma chloride 115 mmol/L
- Plasma bicarbonate 16 mmol/L
1 What is the diagnosis?
(a) Type I (distal) renal tubular acidosis
(b) Type II (proximal) renal tubular acidosis
(c) Type IV renal tubular acidosis
(d) Bartter’s syndrome
(e) Gittleman’s syndrome
2 Suggest two abnormalities which might be seen on a plain radiology:
(a) Small renal outlines
(b) Horseshoe kidney
(c) Renal calculi
(d) Sloughed renal medullary papillae
(e) Brown tumours
(f) Greenstick fractures
(g) Looser’s zones
(h) Subchondral erosions
(i) Osteitis ﬁbrosa et cystica
(j) Erosion of subendostial bone on ulnar aspect of hand bones
2 (c), (g)
2 (c), (g)
Grasp the concept in this clinical vignette for both USMLE and MRCP.
In renal tubular acidosis (RTA) there is a failure to acidify urine to a level appropriate for blood pH; systemic acidosis is therefore not corrected. Unlike renal failure, anions such as sulphate and phosphate are filtered normally and are therefore unavailable to balance the loss of bicarbonate; electrical neutrality is instead maintained by renal chloride absorption, resulting in a hyperchloraemic metabolic acidosis with a normal anion gap.
In proximal (type II) RTA, there is a diminished renal bicarbonate threshold because bicarbonate reabsorption in the proximal tubules is incomplete. The increased urinary bicarbonate excretion lowers the plasma bicarbonate concentration until a new
steady state is reached. At this stage the urine is free of bicarbonate and has an acid pH to match the systemic acidosis. Proximal RTA in its primary form usually presents in infants with failure to thrive, polyuria and growth retardation. Secondary forms may occur in patients with generalized proximal tubular damage due to cystinosis, Wilson’s disease or myeloma, and after renal transplantation. There is no metabolic bone disease and nephrocalcinosis is unusual. The pathophysiology of distal (type I) RTA is complex, but can be thought of in simple terms as a failure of hydrogen ion secretion in the distal tubules. The urine is therefore never acid, even in the presence of systemic acidosis. The systemic acidosis reduces tubular reabsorption of calcium, resulting in hypercalciuria and secondary hyperparathyroidism: nephrocalcinosis and bone disease are therefore characteristic.Distal RTA is most commonly a dominantly inherited condition. In both disorders acidosis provokes potassium loss and hypokalaemia, and patients often complain of weakness as a result. The diagnosis of distal RTA can be made in a patient with a hyperchloraemic metabolic acidosis and a urinary pH above 5.5. If acidosis is mild or absent, an ammonium chloride loading test may be necessary. Normal individuals should lower their urinary pH to below 5.5; patients with distal RTA will not. Proximal tubular acidosis should be considered especially in patients with hyperchloraemic acidosis and associated features such as glycosuria and aminoaciduria. If the metabolic acidosis is severe enough, an early morning urine of pH 5.5 or less supports the diagnosis. If a low urinary pH is not found, an ammonium chloride test should be performed to exclude the diagnosis of distal RTA. A deﬁnitive diagnosis can be made by bicarbonate titration. The characteristic ﬁnding is an elevated urinary excretion of bicarbonate in the face of a normal plasma bicarbonate. This patient has distal RTA as the urine pH is high despite systemic acidosis, and because there is clinical evidence of bone disease and nephrocalcinosis.