RTA Flashcards
What is RTA?
This describes a group of hyperchloraemic metabolic acidosis occurring secondarily to an abnormality in urinary acidification
What is the principle abnormality in RTA?
Loss in bicarb results in low serum Na conc
How is the prinicple abnormality compensated for? Relate to anion gap.
Need to compensate electrochemical loss by increasing serum chloride to restore electroneutrality. Reflected in the anion gap as it remains unchanged
How is bicarbonate reabsorbed in the PCT?
By excreting an H+ via a Na-H antitransporter (NHE3). HCO3 combines with H to make carbonic acid to dissociate into water and CO2 (catalysed by carbonic anhydrase IV). CO2 and water is reabsorbed passively. Recombine in the PT cell to make carbonic acid via carbonic anhydrase II. Cabonic acid dissociates into HCO3 and H. 3xBicarb enters blood with 1xNA (NBC1)
Describe type I RTA
Characterised by the inability of the distal tubular secretion of H+ and, thus, inability to lower pH<5.5 in systemic acidaemia. It can be inherited or acquired disorder.
Biochemical features of RTA I
Hypokalaemia (renal potassium wasting to maintain electroneutrality), nephrocalcinosis, and urolithiasis
What causes RTAI to lose ability to secrete H+?
Two mechanisms
Secretory
- inability to create and maintain H+ gradient across luminal membrane
Back-leak
- inability to secrete H+ remains but a gradient cannot be maintained due to H+ back diffusion
What is the difference between primary and secondary forms?
Primary inherited
Secondary acquired
Primary RTAI
Autosomal dominant
- mutation in SLC4A1 which encodes for the AE1 anion exchanger that mediates the bicarbonate exit from the alpha-intercalated cells
Autosomal recessive
- utation in ATP6V1B1 or ATP6V0A4 which encodes for the B1 and A4 subunits of the H+ ATPase
Secondary RTAI
Due to a range of diseases or drugs. Caused by
- autoimmune disease: systemic lupus erythematosus, rheumatoid arthritis
- tubulointerstitial disease: chronic interstitial nephritis, obstructive uropathy
- hypergammaglobulinemia: multiple myeloma, chronic liver disease
- Drugs: lithium, NSAID, antivirals
What is incomplete distal RTA?
Do not present metabolic acidosis, but lack the ability to produce acidified urine following acid load
What causes incomplete distal RTA?
Increased excretion of NH4+ balances acid base abnormality caused by renal inability to excrete H+.
Low urinary citrate and elevated calcium promote nephrocalcinosis and urolithiasis
What is RTA II?
Proximal RTA characterised by the impaired bicarbonate reabsorption in the proximal tubules and subsequent self-limiting urinary loss
- has an intact H+ secretion meaning ability to form acidified urine is present.
- Inherited or aquired
Primary RTAII
- mutations in SLC4A4 which encodes a NBC1, a mutation which associate with short stature and ocular abnormalities
- Others: inherited conditions causing RTAII are cystinosis, tyrosinaemia, glactosaemia, Wilsons disease
Secondary RTAII
Here a range of toxins (heavy metals), drugs and other disorders (multiple myeloma, vit D deficiency) can cause the development of RTA II.
What is RTAIV?
Distal RTA with mineralocorticoid deficicency.
- aldosterone deficiency or the tubular resistance to its actions
- urine acidification is intact, but exretion of NH4 is subnormal
- present with hyperkalaemia
Cause of reduced aldosterone and resistance in RTAIV?
Reduced aldosterone production causing the disorder can be due to hyporeninaemic hypoaldosteronism (renal disease, NSAIDs), angiotensin pathway disruption (ACEi), adrenal insufficiency or inherited disorders.
Resistance caused by ENaC inhibition (spironolactone, eplerenone) or pseudohypoladosteronims type I
What needs to be excluded when diagnosing RTA?
Common causes of normal anion gap metabolic acidosis such as GI bicarbonate loss
What biochemical tests are useful in investigating RTA?
U&E to make an anion gap
- Anion gap is used to estimate urinary NH4 excretion
What does the anion gap tell you in RTA investigations?
- negative AG indicates increase NH4 excretion - seen in RTA II
How is the urine osmolar gap used?
Same function as AG: estimate NH4 excretion
- urine osmolar gap>100 indicates increased urinary excretion of NH4+ - thus RTA II
What calculation can be done using a paired serum and urine sample?
Fractional bicarbonate excretion
- >10-15% indicates RTA II
How is the trans-tubular potassium gradient used in RTA diagnosis?
Used to estimate the glucorticoid activity in suspected type 4 RTA
- > 10 in hyperkalaemia
- <7 suggest lack of aldosterone
What dynamic function test is available?
Ammonium chloride loading test: Test kidneys ability to deal with acid load
- Ammonium chloride is administered orally over 2h. Urine will be collected every hour for 6 hours for pH measurement
- RTAI has urine pH <5.5
