Describe the biochemical consequences of renal tubular ...



Describe the biochemical consequences of renal tubular acidosis and the laboratory investigation of the condition. (March 05, Paper 2, Question 2)

Examiners Comments: There were some very good answers to this question. However, the terminology seems to have muddled some candidates. A lot mixed up type 1 and 2.

Plan:

Define RTA

Main characteristics

Classification of types and their features

Investigation

Flow chart

Routine tests

Dynamic function tests

Summary

Renal tubular acidosis (RTA) is a group of both inherited and acquired disorders affecting the ability of the renal tubules to secrete hydrogen ions or retain bicarbonate. They are characterised by a hyperchloraemic, normal anion gap, metabolic acidosis with a urinary bicarbonate or hydrogen ion excretion that is inappropriate for the plasma pH. Typically the GFR is normal (or slightly low) and there is no retention of anions such as phosphate or sulphate (as opposed to the acidosis of renal failure)

Classification

There are 3 main types of RTA that have been identified

1. distal RTA – type I

2. proximal RTA – type II

3. RTA secondary to aldosterone deficiency or resistance – type IV

Distal RTA (Type I)

The primary abnormality in distal RTA (dRTA) is a failure to lower urine pH (below pH 5.5) in the presence of systemic acidosis due to impaired distal tubular H+ secretion.

It occurs most often in infants (often transiently) or young children, but it may be encountered in adults.

Most cases present with metabolic acidosis frequently accompanied by hypokalaemia, nephrocalcinosis, muscle weakness and urolithiasis. This type of RTA is often associated with bone diseases such as rickets and osteomalacia, hypercalciuria may be seen due to increased bone resorption, leading to stone formation.

Several subtypes may be seen:

- Secretory dRTA (Classic) – inability to create and maintain H+ ion gradient across the luminal membrane

- Back-leak dRTA – the kidney tubules ability to secrete H+ ions is retained, but the gradient is not maintained due to back diffusion. Typically this occurs in association with specific drug treatments

- Voltage-dependent dRTA – due to an inability to maintain a negative intraluminal negative potential and thus promote H+ ion (and potassium) secretion. This subtype of dRTA has many features in common with type IV RTA, the key difference is the in voltage dependent dRTA, patients cannot lower the urine pH in response to an acidosis.

NB. This subtype of dRTA is also associated with HYPERKALAEMIA (secretory and back-leak dRTA are associated with HYPOkalaemia). This is because of impaired NH4+ excretion secondary to decreased trapping of NH3 in the collecting duct due to the H+ ion secretion defect.

- Incomplete dRTA – this is a less severe, normokalaemic form which may represent an early stage of overt dRTA

Proximal RTA (Type II)

The primary abnormality in proximal RTA (pRTA) is a failure of bicarbonate resorption, which may occur as either an isolated defect (primary or sporadic) that occurs primarly in infant males and is associated with growth retardation. More commonly, pRTA in association with generalised proximal tubular disorders (i.e. Fanconi syndrome). Therefore, the biochemical features of the generalised tubular disorder may be present (such as glycosuria, aminoaciduria, hyperphosphaturia and hypophosphataemia in Fanconi syndrome).

In all types of pRTA, the threshold for bicarbonate is reduced from a serum concentration of 22mmol/L to approx. 15mmol/L. Once the bicarbonate falls below this threshold, the filtered bicarbonate is reclaimed and the urinary pH will generally be ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download