L27 Renal tubular acidosis Flashcards
(33 cards)
What is the definition renal tubular acidosis?
All belongs to normal anion-gap/ high anion-gap metabolic acidosis?
Definition:
- defect in the ability of renal tubule to respond to academia appropriately
NAGMA
possible aetiologies
1. can be due to loss of bicarbonate/bicarbonate precursors
e.g. diarrhoea, type 2 (proximal) renal tubular acidosis (RTA)..
- decreased renal acid excretion
e. g. type 1 (distal) RTA, type 4 RTA (hypoaldosteronism)
Normal physiology at the proximal tubules?
a) lumen
b) blood
a) lumen
- H+ leaves nephrons to lumen via Na/H exchange channels (H+ leaves, Na+ in)
> H+ becomes H2CO3 and releases CO2 and H2O
- CO2 enters back to proximal tubule
b) blood
- Na+ and HCO3- into blood
- Na+/K+ ATP channels; 3Na to blood, 2K+ into nephrons
Type 2 RTA:
when HCO3- not co-absorbed with Na+ into blood > Na+ won’t be reabsorbed into cell from lumen in exchange with H+, H+ remains to be at cell?
Normal physiology at the cortical collecting tubules?
a) lumen
b) blood
a) lumen
- H+ ATPase out to lumen
- H+/K+ ATP channels: H+ out to lumen, K+ into renal cells
b) blood
- HCO3- into blood, Cl- to nephrons
- Na+/K+ ATP channels; 3Na to blood, 2K+ into nephrons
Name the locations of defects of Type 1, Type 2 and Type 4 renal tubular acidosis respectively.
Type 1: distal tubules
Type 2: proximal tubules
Type 4: Adrenal/renal tubules (hyperkalemic)
State the pathophysiology of Type 1, Type 2 and Type 4 renal tubular acidosis respectively.
Type 1: impaired distal urine acidification
Type 2: reduced proximal HCO3- reabsorption at apical membrane
Type 4: Aldosterone deficiency/ tubular resistance to aldosterone > no Na+ absorbed > hyperkalemia, more H+ (?)
What are the causes to Type 1 renal tubular acidosis? (2)
Distal tubule
- Primary
- persistent (sporadic/AD/with neurosensorial deafness in AR inherited disease)
(genetic mutation in H+ ATPase PUMP of alpha intercalated cells) - Secondary
- Hypercalciuria (e.g. hyperparathyroidism)
- Amyloidosis
- Autoimmune (e.g. SLE, RA, Sjogren’s syndrome - damage distal and collecting tubules)
- Drugs (e.g. amphotericin B - anti-fungal, lithium)
Causes of Type 2 renal tubular acidosis?
- Primary isolated defect
- Secondary
- Fanconi syndrome**: generalised proximal tubular dysfunction (unable to absorb a lot of electrolytes)
- drugs (e.g. aminoglycosides, tenofovir)
Causes of Type 4 renal tubular acidosis?
- Primary
- transient - Secondary
i. hypoaldosteronism
(hyporeninaemic: diabetic nephropathy
hyperreninaemic: Addison’s disease)
ii. pseudohypoadosteronism
(genetics, chronic interstitial nephropathies)
iii. drug induced hyper K
(e.g. ACEI, beta-antagonist)
Which of the following about Type 1 Renal tubular acidosis is incorrect?
A. Acidaemia is the most serious among all
B. Plasma HCO3- is <10 mmol/L
C. Urine pH is >5.5
D. It causes hyperkalemia
E. Urine anion gap is positive
F. Urine osmolal gap is <150 mOsm/kg
G. It increases risk for calcium phosphate kidney stones
D
it causes hypokaleimia
C: higher other other types, because H+ are not excreted
G: metabolic acidosis increases urine Ca2+ excretion, thus cause an increase in Ca2+ by bone turnover > increases this risk
Which type(s) of RTA are associated with poor growth/ osteomalacia?
Type 1 and Type 2 RTA
List the clinical features of type I RTA. (4)
- Osteomalacia: Hypercalceuria due to reduced H+ secretion
- Nephrocalcinosis, nephrolithiasis: due to hypercalciuria + alkaline urine
- Muscle weakness: hypoK
- Polyuria
What is the gold standard for Type I RTA?
NH4+ loading test
- ~ acid load
- normal: urine pH <5.5
- Type I RTA: Urine pH >5.5 (impaired distal urine acidification)
What is the gold standard for Type 2 RTA?
HCO3- loading test
- normal: unchanged urinary HCO3-
- Type 2 RTA: Urine pH >7.5 with FEhco3- >15% (fractional excretion) [reduced proximal HCO3- reabsorption]
Which of the following about Type 2 Renal tubular acidosis are incorrect?
A. Urine pH is <5.5 B. Hypokalemia C. Urine anion gap is negative D. Urine osmolal gap >150 mOsm/kg E. Alkali therapy can improve hypo K
A and E are incorrect
A:
Urine pH varies!
<5.5 when urine is acidified by normal distal alpha-intercalated cells
>5.5 if exceeds reabsorption threshold (in HCO3- loading test)
B: because HCO3- not reabsorbed, osmotic diuresis > RAAS > hypokalaemia
Type IV RTA causes hypo/hyperkaelemia? Why?
Hyperkalemia
- no RAAS > Na+ reduced, K+ increases in blood
Which of the following about Type 4 Renal tubular acidosis are incorrect?
A. Urine pH is <5.5
B. reduced effect on H+/ATPase in alpha intercalated cells thus reduced H+ excretion, causing acidemia
C. Urine anion gap is negative
D. Urine osmolal gap >150 mOsm/kg
E. there is reduced ammonium excreted in urine
C and D are wrong
- Urine anion gap is positive
- Urine osmolal gap < 150 mOsm/kg
E: because bonded with H+?
Management for patient with Type I RTA?
How does it help?
Alkaline therapy can improve hypoK
Effect of giving alkali therapy:
- Increased NaHCO3 distal delivery raises urine pH and allows more H to be secreted
- Expands ECV > ↓aldosterone and thus ↓Na reabsorption > Resolves hypokalemia
Management for patient with Type 2 RTA?
Alkali therapy (e.g. NaHCO3) must prescribe with K supplements
(because baseline hyperaldosteronism + distal HCO3 load in Type II RTA will further increase K secretion)
Management for patient with type 4 RTA?
- Withdraw K retaining drugs
- Restrict dietary K
- Diuretics
- Fludrocortisone (mineralocorticoid effect)
What is Fanconi syndrome and what are its causes? (3)
Fanconi syndrome
- generalised proximal tubular dysfunction
(- a cause of type II RTA)
Causes
- Multiple myeloma
- Wilson’s disease
- Lead poisoning
What can patients with Fanconi’s syndrome presented with? (6)
Presentations:
- bicarbonaturia
- glucosuria
- phosphaturia
- uricosuria
- aminoaciduria
- tubular proteinuria
Investigations for RTA?
- state what is ruled out in each investigation. (5)
- Plasma K
- Hyperkalemia - type 4 - Urine for glucose and amino acids
- Fanconi’s syndrome - type 2 - Bicarbonate infusion test - FEhco3 > 15% in proximal RTA - type 2
- USG urinary tract
- nephrocalcinosis in distal RTA - type I - Urine pH, Urine osmolar gap, urine anion gap
Algorithm
NAGMA > 1st investigation?
Plasma K
- if hyper = type 4
- if hypo = others
Algorithm
If plasma K checked: hypokalaemia - check what?
Urinary pH
- Urinary pH >5.5 = type 1 RTA
- <5.5
= diarrhea/ type 2 RTA/ carbonic anhydrase inhibitors
