An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications): Type Type 1 Type 2 Type 4 Location Collecting Tubules, distal tubules Proximal tubules Adrenal Acidemia Yes (very severe) Yes Mild when present Potassium Hypokalaemia Hypokalemia Hyperkalemia Pathophysiology Failure of α intercalated cells to secrete H+ and reclaim K+ Failure of proximal<unk>  cells to reabsorb Deficiency of aldosterone, or a resistance to its effects, (hypoaldosteronism or pseudohypoaldosteronism) Type 1: distal Distal<unk>  (dRTA) is the classical form of<unk> , being the first described. Distal<unk>  is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated cells of the medullary collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because<unk>  excretion is the primary means of eliminating from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H+ while cannot be reclaimed by the cell, leading to acidemia (as builds up in the body) and hypokalemia (as cannot be reabsorbed by the alpha cell). This leads to the clinical features of dRTA; In other words, the intercalated cells' apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other<unk>  types. * Normal anion gap metabolic<unk> /acidemia * Hypokalemia, Hypocalcemia, Hyperchloremia * Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate). * Nephrocalcinosis (deposition of calcium in the substance of the kidney) * Bone demineralisation (causing rickets in children and osteomalacia in adults) * Growth deficiency * Medullary cysts * Sensorineural hearing loss * Hereditary hemolytic anemia Distal<unk>  has also been linked to specific genetic mutations that will alter when the disease will present in the patient's life. Patient's with mutations in ATP6V1B1 and ATP6V0A4 will present with symptoms within the first year of life, while those with mutation of the SLC4A1 have delayed onset around 10 years of age. Electrolyte imbalances remain the same, while in severe cases symptoms can advance to amino aciduria and hyperammonemia. In a large Asian series of Distal<unk>  in Sjogren's Syndrome, late diagnosis is a rule in spite of overt hypokalemic periodic paralysis in a vast majority of them dRTA is the most common form of<unk>  diagnosed in Western countries, and can be classified as either hereditary (primary) or acquired (secondary). Primary<unk>  generally results from systemic and autoimmune diseases or drug and toxin exposure in adults, whereas pediatric<unk>  results from genetic defects in the proteins that facilitate urine acidification at the distal tubule. Hereditary dRTA generally presents as failure to thrive during the first several months of life. Other common clinical manifestations in children include a variety of gastrointestinal and urinary symptoms, including polyuria, polydipsia, constipation, diarrhea, bouts of dehydration, and decreased appetite. Type 2: proximal Radiograph of a child with rickets, a complication of both proximal and, less commonly, distal<unk> . Proximal<unk>  (pRTA) is caused by a failure of the proximal<unk>  cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. Reabsorption of bicarbonate is typically 80-90% in the proximal tubule and failure of this process leads to decreased systemic buffer and metabolic<unk> . The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the alpha intercalated cells can produce H+ to acidify the urine to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalized dysfunction of the proximal<unk>  cells called Fanconi syndrome, in which there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and<unk>  proteinuria. The principal feature of Fanconi syndrome is bone demineralization (osteomalacia or rickets) due to phosphate wasting. Type 3: combined proximal and distal In some patients,<unk>  shares features of both dRTA and pRTA. This rare pattern was observed in the 1960s and 1970s as a transient phenomenon in infants and children with dRTA (possibly in relation with some exogenous factor such as high salt intake) and is no longer observed. This form of<unk>  has also been referred to as juvenile<unk> . Combined dRTA and pRTA is also observed as the result of inherited carbonic anhydrase II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis,<unk> , cerebral calcification, and mental retardation. It is very rare and cases from all over the world have been reported, of which about 70% are from the Maghreb region of North Africa, possibly due to the high prevalence of consanguinity there. The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification. Type 3 is rarely discussed. Most comparisons of<unk>  are limited to a comparison of types 1, 2, and 4. Type 4: absolute hypoaldosteronism or aldosterone insensitivity Type 4<unk>  is due either to a deficiency of Aldosterone, or to a resistance to its effects. Type 4<unk>  is not actually a<unk>  disorder at all nor does it have a clinical syndrome similar to the other types of<unk>  described above. It was included in the classification of<unk>  as it is associated with a mild (normal anion gap) metabolic<unk>  due to a physiological reduction in proximal<unk>  ammonium excretion (impaired ammoniagenesis), which is secondary to hypoaldosteronism, and results in a decrease in urine buffering capacity. Its cardinal feature is hyperkalemia, and measured urinary acidification is normal, hence it is often called hyperkalemic<unk>  or<unk>  hyperkalemia. Causes include: * Aldosterone deficiency (hypoaldosteronism): Primary vs. hyporeninemic (including diabetic nephropathy) * Aldosterone resistance # Drugs: NSAIDs, ACE inhibitors and ARBs, Eplerenone, Spironolactone, Trimethoprim, Pentamidine # Pseudohypoaldosteronism
Renal tubular acidosis
Distal renal tubular acidosis
Proximal renal tubular acidosis
Isotonic hyponatremia
Hyperchloremic acidosis
Hypotonic hyponatremia
Cystinuria
Normal anion gap acidosis