Give the causes of normal anion gap metabolic acidosis?
HARD UP AA
Acetozolamide (carbonic anhydrase inhibitor)
Renal tubular acidosis
Ammonium chloride ingestion
What are the 2 main categories od normal anion gap metabolic acidosis?
GI loss of bicarbonate: small bowel secretions in diarrhoea or pancreatic drainage
Renal tubular acidosis
What is type of acidosis do you get with RTA?
Hypokalaemic Hyperchloraemic metaboic acidosis with normal anion gap
What is type 1 RTA due to?
Inability to excrete H+
Where does type 1 RTA occur?
What is the urinary pH in RTA1?
Over 5.5 (ie failure to acidify urine)
What are the clinical features of RTA1?
1. Rickets/osteomalacia due to buffering of H+ with calcium in bone
2. nephrocalcinosis with renal calculi leading to recurrent UTI
Why do you get renal stones in RTA1?
Hypercalciuria from bone
Decreased urinary citrate: as reabsorbed from urine as a buffer for H+
All favour calcium phosphate stone formation
How is type 1 RTA diagnosed?
1. Urinary pH > 5.3 in face of systemic acidosis
2. failure to acidify urine following an oral acid load challenge: alluminium chloride test
What is the treatment of type 1 RTA?
Sodium bicarbonate or citrate
correct the acidemia and reverse bone demineralisation.
What is the cause of type 1 RTA?
Autoimmune: Sjogren’s, SLE
What is type 2 RTA due to?
Inability to reabsorb bicarbonate (bicarb leak)
Where does type 2 RTA occur?
What are the causes of type 2 RTA?
Tubulointerstitial disease: myeloma
What type of acidosis do you get with type 2 RTA?
Hypokalaemic, hyperchloraemic metablic acidosis
Normal anion gap
What is the difference in the urine between type 1 and type 2 RTA?
In type 2: tubules are able to reabsorb SOME HCO3
So urine can acidify during systemic acidosis
Which syndrome is type 2 RTA associated with?
Fanconi syndrome (generalised dysfunction of proximal tubule cells)
Which is more common type 1 or type 2 RTA?
Why is hypokalaemia common in type 2 RTA?
Due to osmotic diuretic effect of reduced HCO3 reab increased flow rate to distal tubule increased K+ excretion
How is type 2 RTA diagnosed?
Iv sodium bicarbonate load: if see high fractional excretion (>15%) of HCO3 = type 2 RTA
What is the treatment of type 2 RTA?
High doses of bicarbonate (often intolerable)
What is type 3 RTA?
Combination of type 1 and 2 RTA
What is the difference between type 4 RTA and type 1 and 2?
What is type 4 RTA due to?
Why do you get acidosis in type 4 RTA?
Low aldosterone causes hyperkalaemia and acidosis
As it decreases K+ and H+ secretion
What are the functions of aldosterone?
1. acts on nuclear mineralocorticoid receptors (MR) in distal tubule and collecting duct in kidney to activate Na/K/ATP pump on basolateral membrane of cell. So sodium is reabsorbed into the blood and K+ is secreted into the urine
2. upreg EnaC on apical membrane to increase permeability of Na
3. Cl- reab with Na to maintain electrochemical balance