L27 Renal tubular acidosis Flashcards
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
Why is urine ammonia useful in RTA investigations?
- At distal tubules, H+ are secreted as NH4+ (as buffer)
- assessment of Urinary NH4+ is useful for investigation of NAGMA/hyperchloraemic metabolic acidosis
What is urine anion gap? (equation)
Una + Uk - Ucl (normalL 20-90 mmol/L)
Why UAG decreases in NAGMA RTA with intact acidification mechanism ?
UAG= Una + Uk - Ucl
In NAGMA with intact acidification mechanism (e.g. proximal RTA), Unh4 is accompanied by a parallel increase in Ucl.
Increased H+ secretion Increased NH4 (urine buffering) and Cl- accompanies Negative UAG
When will UAG increase in RTA?
When acidification is impaired
e. g. NH4 loading test
- in distal RTA, type 4 RTA, CKD
Which of the followings are limitations of using urinary anion gap to make a diagnosis?
A. False+ in unmeasured anions in urine, e.g. ketoacids, hippurate (as toluene toxicity)
B. Invalidated in volume depletion
Both
B: reduce distal Na delivery impairs distal acidification
What is UOG (urine osmolar gap)? (calculation)**
Measured Uosm - Calculated Uosm (= 2x [Una + Uk]+ Uurea + Uglucose)
Why? (read if don’t understand the calculation)
Under most conditions, the urine osmolality is generated by Na+, K+, urea, glucose (if present), and ammonium salts. Thus, if the urine osmolality is actually measured and calculated using the measured concentrations of Na+, K+, urea, and glucose (if present), the difference should represent the concentration of ammonium salts.
What is the normal Urine osmolar gap?
10-100mOsm/kg
UOG <150 mOsm/kg in metabolic acidosis suggest?
low ammonium (Unh4) = distal RTA
(repeated:
Under most conditions, the urine osmolality is generated by Na+, K+, urea, glucose (if present), and ammonium salts. Thus, if the urine osmolality is actually measured and calculated using the measured concentrations of Na+, K+, urea, and glucose (if present), the difference should represent the concentration of ammonium salts.)
Which of the following will affect urine osmolar gap?
A. increased of unmeasured anions in urine
B. urease-producing bacterial UTI
C. urinary osmotically active substance (e.g. ethanol, mannitol)
Measured Uosm - Calculated Uosm (= 2x [Una + Uk]+ Uurea + Uglucose)
B & C only
B: increase in NH4
A: anions are not in the equation?
