RENAL TUBULAR

ACIDOSIS

PROF. DR. ABDUL MANAN JUNEJO

HEAD OF NEPHROLOGY DEPARTMENT
JPMC/JSMU, KARACHI
23/2/2023
 INTRODUCTION

KIDNEY

• Bilateral bean shaped, located in lumbar region.

• Structurally consist of glomeruli, vessels and tubule interstitial
system.
• Tubules regulates acid base system, electrolytes and water
metabolism
 INTRODUCTION

• Lungs and Kidneys are responsible for Normal acid base

balance.
• Alveolar ventilation removes CO2.
• Kidneys reabsorb filtered Bicarbonate and excrete Hydrogen
ion.
• Hydrogen ions are excreted primarily by enhancing the
excretion of ammonium ions in the urine.
 METABOLIC ACIDOSIS

• Loss or decreased production of bicarbonates leads to systemic

acidemia, which produces low arterial ph and low serum hco3
• The appropriate compensation is increased respiration
• leading to a reduced pCO2.
 Anion-Gap

• This Gap refers to the difference between the concentration of

Cations (Na+ ,k+)and concentration of Anion (Cl- and HCO3-
)in the blood.
• Anion gap = Na - (Cl + HCO3)
• Normal values 09 - 14mEq/L.
 Differential Diagnosis of High AG
Metabolic Acidosis

• Methanol
• Ethylene glycol
• Uremia
• Diabetic Ketoacidosis
• Paraldehyde
• INH
• Lactic acidosis
• Salicylates
 Non-anion gap Metabolic Acidosis

• Uretero-Sigmoid Diversions
• Saline administration
• Endocrinopathies
• – Addisons, Spirinolactone, Triamterene,
Amiloride, Primary Hyperparathyroidism
• Diarrhoea
• hyper-Alimentation
• Renal Tubular Acidosis
 Renal Tubular Acidosis
DEFINITION
• Renal tubular acidosis (RTA) is a disease state characterized
by a normal anion gap (hyperchloremic) metabolic acidosis in
the setting of normal or near-normal glomerular filtration rate
with defects in tubular H secretion & urinary acidification
 Incidence

• Predominant age: All ages

• Predominant sex: Male > Female (with regard to type II RTA
with isolated defect in bicarbonate reabsorption)
 TYPES

• Distal / type 1 RTA

• Proximal / type 2 RTA
• Hyporeninemic/Hypoaldosteronism / type 4 RTA
 Type 1-Distal RTA
• Distal RTA (dRTA) is the classical form of RTA. Inability of
the distal tubule to acidify the urine.
• Due to impaired hydrogen ion secretion
• Urine pH >5.5.
 Pathophysiology

• Renal excretion is the primary means of eliminating

acid from the body.
• Failure of acid secretion by distal Nephron.
• It leads to an inability to acidify the urine to a pH
<5.3.
• There is an inability to excrete H+,while K+ cannot
be reabsorbed, leading to acidemia and hypokalemia .
• The substance of the kidney develops stones
bilaterally.
 Risk Factors

• Genetics
• Autosomal dominant or recessive.
• Autosomal recessive form is associated with sensorineural
deafness.
 ETIOLOGY
• Genetic • Wilson disease
• Sporadic • Obstructive Uropathy
• Autoimmune diseases: • Chronic pyelonephritis
rheumatoid arthritis (RA), SLE • Chronic Renal Transplant
• Hematologic diseases: rejection
Sickle cell disease, hereditary
elliptocytosis
• Medications:
Amphotericin B, lithium, K+-
sparing diuretics
• Toxins:
Toluene, glue
• Vitamin D intoxication
 CLINICAL MANIFESTATIONS

• Non-anion gap metabolic Acidosis

• Growth failure
• Nephrocalcinosis
• Hypercalciuria
 Type 2-Proximal RTA

• Defect of the proximal tubule in bicarbonate (HCO3)

reabsorption.
• Urine usually pH <5.5.
• Leading to urinary bicarbonate wasting and subsequent
Acidemia.
• The distal cells function normally, so the acidemia is less
severe than dRTA and the urine can acidify to a pH <5.3.
• It is usually associated with a generalized dysfunction of the
proximal tubular cells called Fanconi's syndrome.
 Clinical manifestations

• Phosphaturia
• Glycosuria
• Aminoaciduria and uricosuria
• Tubular proteinuria
• Bone deminerlaization due to phosphate wasting
 Risk Factor

• GENETICS
• Autosomal dominant form is rare.
• Autosomal recessive form is associated with ophthalmologic
abnormalities and mental retardation.
 Etiology

• Diseases associated with Fanconi syndrome

• Sporadic
• Multiple myeloma
• Heavy-metal poisoning
• Medications: Acetazolamide, sulfanilamide, ifosfamide,
outdated tetracycline, topiramate
• Interstitial renal disease
• Nephrotic syndrome
• Congenital heart diseases
 Clincal manifestation
• Growth failure in the 1st year of life
• Polyuria
• Dehydration
• Anorexia
• Vomiting
• Constipation
• Patients with primary Fanconi syndrome will have additional
symptoms.
 Type 4 RTA

• Due to Aldosterone resistance or deficiency that results in

hyperkalemia.
• Due to a physiological reduction in proximal tubular
ammonium excretion (impaired ammoniagenesis),
• Secondary to Hypoaldosteronism and results in a decrease in
urine buffering capacity.
• Urine pH <5.5.
 Etiology
• Medications: NSAIDS, ACE inhibitors,ARBS,
heparin, calcineurin inhibitors (tacrolimus,
cyclosporine),
• Diabetic nephropathy
• Obstructive nephropathy
• Nephrosclerosis due to hypertension
• Tubulointerstitial nephropathies
• Primary adrenal insufficiency
• Sickle cell nephropathy
 Clinical Manifestations

• Polyuria
• Dehydration
• Rarely, with life-threatening hyperkalemia
• Hyperkalemic non-anion gap metabolic acidosis
• Elevated urine sodium levels & inappropriately low urine
potassium levels reflect the absence of Aldosterone effect.
 Diagnosis

• History collection
• Often asymptomatic (particularly type IV)
• Failure to thrive in children
• Renal stones
• Weakness or polyuria (due to hypokalemia)
• Rickets in children
• Osteomalacia in adults
• Constipation
• Polydipsia
• Electrolytes - hyperchloremic metabolic acidosis.
• Normal Anion gap
• Hypokalemia or normokalemia
• Hyperkalemia
• BUN, Creatinine
• Urine Ph and URINE ANION GAP: Inappropriately alkaline
(pH >5.5)
• Urine anion gap: positive in RTA and negative in extra renal
causes
• Urine calcium: High in type I, Typically normal in type II
• A renal ultrasound - to identify underlying structural
abnormalities such as obstructive uropathies as well as to
determine the presence of nephrocalcinosis.
• Correction of the Acidemia with oral sodium
bicarbonate, sodium citrate or potassium citrate.
• This will reverse bone demineralization
• Hypokalemia and urinary stone formation and
nephrocalcinosis can be treated with potassium
citrate tablets
• Patients with Fanconi syndrome generally require Phosphate
supplementation.
• Patients with distal RTA should be monitored for the
development of hypercalciuria.
• May require thiazide diuretics to decrease urine calcium
excretion.
• Patients with type IV RTA may require chronic treatment for
hyperkalemia with sodium-potassium exchange resin.
 Prognosis

• Depends on associated disease, otherwise good with therapy.

• Transient forms of all types of RTA may occur.