RTA PPT

1. RENAL TUBULAR
ACIDOSIS
Dr. Balkrishna kumar
PGT 1st YEAR DEPARTMENT ON
MEDICINE

2. 2
RENAL TUBULAR ACIDOSIS
• Renal tubular acidosis (RTA) is applied to a
group of transport defects in the reabsorption
of bicarbonate (HCO3-), the excretion of
hydrogen ion (H+), or both.
• The RTAsyndromes are characterized by a
relatively normal GFR and a metabolic
acidosis accompanied by hyperchloremia and a
normal plasma anion gap.

3. • Anion gap = [Na+] – {[Cl–] + [HCO3–]}
• normal AG : 8-16 mEq/L
• Predominant unmeasured anions
include albumin , phosphate, sulfate
and organic anions.
• Major unmeasured cations include
calcium, magnesium, potassium and
gamma globulins.

4. ACID LOADS
Ammonium chloride
Hyperalimentation
Ketoacidosis with renal
ketone loss
Bicarbonate Losses
Diarrhea
Pancreatic, biliary, or small
bowel drainage
Ureterosigmoidostomy,
Jejunal or ileal LoopDept of
Urology,
DRUGS
Cholestyramine
Calcium chloride
Magnesium sulfate
Post hypocapnia
Defects in Renal Acidification
Proximal: decreased HCO3-
reclamation
Distal: decreased net acid excretion
Primary mineralocorticoid deficiency
Hyperreninemic hypoaldosteronism
Mineralocorticoid - resistant
hyperkalemia
Dilutional
and KMC, Chennai. 6
Hyperchlore
mic
Metaboli
c
Acidos
is
(Norm
al
Anio
n
Gap
)

5. 5
OBJECTIVES
• Physiology of Renal acidification.
• Types of RTAand characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

6. 6
Physiology of Renal Acidification
• Kidneys excrete 50-100 meq/day of non carbonic
acid generated daily.
• This is achieved by H+ secretion at different levels in
the nephron.
• The daily acid load cannot be excreted as free H+
ions.
• Secreted H+ ions are excreted by binding to either
buffers, such as HPO42- and creatinine, or to NH3 to
form NH4+.
• The extracellular pH is the primary physiologic
regulator of net acid excretion.

7. 7
Renal acid-base homeostasis may be broadly
divided into 2 processes
3
1. Proximal tubular absorption of HCO -
3
(Proximal acidification)
2. Distal Urinary acidification.
 Reabsorption of remaining HCO - that
escapes proximally.
 Excretion of fixed acids through buffering &
4
Ammonia recycling and excretion of NH +.

8. 8
Proximal tubule physiology
• Proximal tubule contributes to renal
acidification by H+ secretion into the tubular
lumen through NHE3 transporter and by
HCO3- reabsorption.
3
• Approx. 85% of filtered HCO - is absorbed by
the proximal tubule.
• The remaining 15 % of the filtered HCO3- is
reabsorbed in the thick ascending limb and in
the outer medullary collecting tubule.

9. 9
Proximal tubule physiology
Multiple factors are of primary importance in
normal bicarbonate reabsorption
 The sodium-hydrogen exchanger in the
luminal membrane(NHE3).
 The Na-K-ATPase pump
 The enzyme carbonic anhydrase II & IV
 The electrogenic sodium-bicarbonate
cotransporter(NBC-1).

10. .
10

11. 11
Ammonia recycling
• Ammonium synthesis and excretion is one of
the most important ways kidneys eliminate
nonvolatile acids.
• Ammonium is produced via catabolism of
glutamine in the proximal tubule cells.
• Luminal NH4+ is partially reabsorbed in the
thick ascending limb and the NH3 then
recycled within the renal medulla

12. Ammonia Recycling
12

13. 13
• The medullary interstitial NH3 reaches high
concentrations that allow NH3 to diffuse into
the tubular lumen in the medullary collecting
tubule, where it is trapped as NH4+ by
secreted H+.

14. 14
Distal Urinary Acidification
• The thick ascending limb of Henle’s loop
reabsorbs about 15% of the filtered HCO3-
load by a mechanism similar to that present in
the proximal tubule, i.e., through Na+-H+
apical exchange(NHE3).

15. 15
H+ secretion
• The collecting tubule (CT) is the major site of
H+ secretion and is made up of the medullary
collecting duct (MCT) and the cortical
collecting duct (CCT).
• Alpha and Beta-intercalated cells make up
40% of the lining while Principal cells and
collecting tubule cells make up the remainder.

16. 16
• Alpha-Intercalated Cells are thought to be the
main cells involved with H+ secretion in the
CT.
• This is accomplished by an apically placed H+-
K+-ATPase and H+-ATPase with a basolateral
Cl-/HCO - exchanger and the usual basolateral
3
Na+ - K+ ATPase.

17. 17

18. 18
• Beta-Intercalated Cells in contrast to the above
3
have a luminal Cl-/HCO - exchanger and a
basolateral H+-ATPase.
• They play a role in bicarbonate secretion into
the lumen that is later reabsorbed by the CAIV
rich luminal membrane of medullary collecting
duct.

19. • CCT H+ secretion is individually coupled to
Na+ transport. Active Na+ reabsorption
generates a negative lumen potential favoring
secretion of H+ and K+ ions.
• In contrast the MCT secretes H+ ions
independently of Na+.
• Medullary portion of the Collecting duct is
the most important site of urinary
acidification

20. Principal cells
20

21. 21
Aldosterone and Renal acidification
• Favors H+ and K+ secretion through enhanced
sodium transport.
• Recruits more amiloride sensitive sodium
channels in the luminal membrane of the
collecting tubule.
• Enhances H+-ATPase activity in cortical and
medullary collecting tubules.
• Aldosterone also has an effect on NH4+
excretion by increasing NH3 synthesis

22. 22
• H+ secretion, bicarbonate reabsorption and NH4+
production occur at the proximal tubule. Luminal CA
IV is present in the luminal membrane at this site and
in MCT.
• NH4+reabsorption occurs at TAL of loop of Henle
and helps in ammonia recycling that facilitates
NH4+excretion at MCT.
• H+ secretion occurs in the CCT either dependent or
independent of Na availability and in the MCT as an
independent process.

23. 23
TYPES OF RTA
Proximal RTA(type 2)
• Isolated bicarbonate defect
• Fanconi syndrome
Distal RTA(type 1)
• Classic type
• Hyperkalemic distal RTA
Hyperkalemic RTA(Type 4)

24. 24
PROXIMAL RTA
• Proximal RTA(pRTA) is a disorder leading to
HCMA secondary to impaired proximal
reabsorption of filtered bicarbonate.
• Since the proximal tubule is responsible for the
reabsorption of 85-90% of filtered HCO - a
3
defect at this site leads to delivery of large
amounts of bicarbonate to the distal tubule.

25. 25
• This leads to bicarbonaturia, kaliuresis and
sodium losses.
• Thus patients will generally present with
hypokalemia and a HCMA.

26. .
26

27. 27
• Isolated defects in PCT function are rarely
found. Most patients with a pRTAwill have
multiple defects in PCT function with
subsequent Fanconi Syndrome.
• The most common causes of Fanconi
syndrome in adults are multiple myeloma and
use of acetazolamide.
• In children, cystinosis is the most common.

28. • pRTA is a self limiting disorder and fall of
serum HCO3_ below 12 meq/l is unusual, as
the distal acidification mechanisms are intact..
• Urine ph remains acidic(<5.5) mostly but
becomes alkaline when bicarbonate losses are
corrected.
• FEHCO3 increases(>15%)with administration
of alkali for correction of acidosis

29. Cause of hyokalemia in Type 2 RTA
Metabolic acidosis  decreases pRT Na+
reabsorption  increased distal tubule
delivery of Na+ which promotes K+secretion.
The pRTAdefect almost inevitably leads to salt
wasting, volume depletion and secondary
hyperaldosteronism.
The rate of kaliuresis is proportional to distal
bicarbonate delivery. Because of this alkali
therapy tends to exaggerate the hypokalemia.

30. • Patients with pRTA rarely develop
nehrosclerosis or nephrolithiasis. This is
thought to be secondary to high citrate
excretion.
• In children, the hypocalcemia as well as the
HCMA will lead to growth retardation, rickets,
osteomalacia and an abnormal vitamin D
metabolism. In adults osteopenia is generally
seen.

31. DISTAL RTA
• Distal RTA(dRTA) is a disorder leading to HCMA
secondary to impaired distal H+ secretion.
• It is characterized by inability to lower urine ph
maximally(<5.5) under the stimulus of systemic
acidemia. The serum HCO3- levels are very low
<12 meq/l.
• It is often associated with hypercalciuria,
hypocitraturia, nephrocalcinosis, and
osteomalacia.

32. • The term incomplete distal RTAhas been proposed to
describe patients with nephrolithiasis but without
metabolic acidosis.
• Hypocitraturia is the usual underlying cause.
Hypocitraturia results from
• increased citrate utilization in proximal tubule cells
due to intracellular acidosis, resulting in an
increased gradient for tubular reabsorption,
• due to the high luminal pH favoring
conversion of citrate3- to the readily
reabsorbable citrate

33. • The most common causes in adults are
autoimmune disorders, such as Sjögren's
syndrome, and other conditions associated
with chronic hyperglobulinemia.
• In children, type 1 RTAis most often a
primary, hereditary condition.

34. Secretory defects causing Distal RTA

35. Non secretory defects causing Distal RTA
• Gradient defect: backleak of secreted H+
ions. Ex. Amphotericin B
• Voltage dependent defect: impaired distal
sodium transport ex. Obstructive uropathy,
sickle cell disease, CAH, Lithium and
amiloride etc.
• This form of distal RTAis associated with
hyperkalemia(Hyperkalemic distal RTA)

36. • A high urinary pH (5.5) is found in the
majority of patients with a secretory dRTA.
• Excretion of ammonium is low as a result of
less NH +trapping. This leads to a positive
urine an4
ion gap.
• Urine PCO2 does not increase normally after a
bicarbonate load reflecting decreased distal
hydrogen ion secretion.
• Serum potassium is reduced in 50% of
patients. This is thought to be from increased
kaliuresis to offset decreased H+ and H-K-
ATPase activity.

37. Type 4 RTA (Hyperkalemic RTA)
• This disorder is characterized by modest
HCMA with normal AG and associationwith
hyperkalemia.
• This condition occurs primarily due to
decreased urinary ammonium excretion.
• Hypoaldosteronism is considered to be the
most common etiology. Other causes include
NSAIDS, ACE inhibitors, adrenal
insufficiency etc.

38. • In contrast to hyperakalemic distal RTA, the
ability to lower urine ph in response to
systemic acidosis is maintained.
• Nephrocalcinosis is absent in this disorder.

39. Dept of Urology, GRH and KMC,
Chennai.
39
OBJECTIVES
• Physiology of RenalAcidification.
• Types of RTAand characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

40. Lab diagnosis of RTA
• RTAshould be suspected when metabolic
acidosis is accompanied by hyperchloremia
and a normal plasma anion gap in a patient
without evidence of gastrointestinal HCO3-
losses and who is not taking acetazolamide or
ingesting exogenous acid.

41. Functional evaluation of proximal
bicarbonate absorption
Fractional excretion of bicarbonate
• Urine ph monitoring during IV administration
of sodium bicarbonate.
• FEHCO3 is increased in proximal RTA>15%
and is low in other forms of RTA.

42. Functional Evaluation of Distal Urinary
Acidification and Potassium Secretion
• Urine anion gap
• Urine osmolal gap
• Urine ph
• Urine Pco2
• TTKG
• Urinary citrate

43. Urine Anion Gap
• Urine AG = Urine (Na + K - Cl).
• The urine AG has a negative value in most
patients with a normal AG metabolic acidosis.
• Patients with renal failure, type 1 (distal) renal
tubular acidosis (RTA), or hypoaldosteronism
(type 4 RTA) are unable to excrete ammonium
normally. As a result, the urine AG will havea
positive value.

44. • There are, however, two settings in which
the urine AG cannot be used.
• When the patient is volume depleted with
a urine sodium concentration below 25
meq/L.
• When there is increased
excretion of unmeasured anions

45. Urine
ph
• In humans, the minimum urine pH that can be
achieved is 4.5 to 5.0.
• Ideally urine ph should be measured in a fresh
morning urine sample.
• A low urine ph does not ensure normal distal
acidification and vice versa.
• The urine pH must always be evaluated in
conjunction with the urinary NH4+ content to
assess the distal acidification process adequately .
• Urine sodium should be known and urine should
not be infected.

46. Urine Pco2
• Measure of distal acid secretion.
• In pRTA, unabsorbed HCO3 reacts with
secreted H+ ions to form H2CO3 that
dissociate slowly to form CO2 in MCT.
• Urine-to-blood pCO2 is <20 in pRTA.
• Urine-to-blood pCO2 is >20 in distal RTA
reflecting impaired ammonium secretion.

47. TTKG
• TTKG is a concentration gradient between
the tubular fluid at the end of the cortical
collecting tubule and the plasma.
• TTKG= [Urine Kx Plasma osmolality)] ÷
[Plasma K x Urine osmolality]
• Normal value is 8 and above.
• Value <7 in a hyperkalemic patient
indicates hypoaldosteronism.
• This formula is relatively accurate as long as the
urine osmolality exceeds that of the plasma
urine sodium
concentration is above 25 meq/L

48. 48
Urine citrate
• The proximal tubule reabsorbs most (70-90%) of
the filtered citrate.
• Acid-base status plays the most significant role in
citrate excretion.
• Alkalosis enhances citrate excretion, while
acidosis decreases it.
• Citrate excretion is impaired by acidosis,
hypokalemia,high–animal protein diet and UTI.
• < 2mg/kg/day
• Calcium > 4mg/kg/day

49. OBJECTIVES
• Physiology of Renal acidification.
• Types of RTAand characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

50. Dept of Urology, GRH and KMC,
Chennai.
50
OBJECTIVES
• Physiology of Renal acidification.
• Types of RTAand characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

51. Treatment
Proximal RTA
• A mixture of Na+ and K+ salts, preferably
citrate, is preferable.
• 10 to 15 meq of alkali/kg may be required per
day to stay ahead of urinary losses.
• Thiazide diuretic may be beneficial if large
doses of alkali are ineffective or not well
tolerated.

52. Distal RTA
• Bicarbonate wasting is negligible in adults who can
generally be treated with 1 to 2 meq/kg of sodium
citrate or bicarbonate.
• Potassium citrate, alone or with sodium citrate
(Polycitra), is indicated for persistent hypokalemia or
for calcium stone disease.
• For patients with hyperkalemic distal RTA, high-
sodium, low-potassium diet plus a thiazide or loop
diuretic if necessary.

53. Hyperkalemic RTATYPE 4
• Treatment and prognosis depends on the
underlying cause.
• Potassium-retaining drugs should always be
withdrawn..
• Fludrocortisone therapy may also be useful in
hyporeninemic hypoaldosteronism, preferably
in combination with a loop diuretic such as
furosemide to reduce the risk of extracellular
fluid volume expansion.

54. Proximal RTA Distal RTA RTA IV
Type of
Acidosi
s
Hyperchloremic
metabolic
acidosis
Hyperchloremic
metabolic
acidosis
Hyperchloremic
metabolic
acidosis
Serum
Potassiu
m
low low high
Urine pH < 5.5 >5.5 < 5.5
Urine
bicarbonat
e loss
.

55. Feature Type 1 Type 2 Type 4
Nephro-
lithiasis
present absent Absent
Nephro-
calcinosis
present absent Absent
Osteo-
malacia
present present Absent
Growth
failure
+++ ++ +++
Hypokalemic
muscle
weakness
++ + -
Alkali
therapy
Low dose (2
–4 meq/kg)
High dose (
2-14 meq/kg)
Low dose ( 2-
3 meq/kg)
Response to
therapy
good fair fair
Features of the RTA
Syndromes