Renal tubular acidosis Totally Explained

Everything about Renal Tubular Acidosis totally explained

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately the urine. When blood is filtered by the kidney, the passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by failure to recover sufficient (alkaline) bicarbonate ions from the filtrate in the early portion of the nephron (proximal tubule) or by insufficient secretion of (acid) hydrogen ions into the latter portions of the nephron (distal tubule). Although a metabolic acidosis also occurs in those with renal insufficiency, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes.
The word acidosis refers to the tendency for RTA to lower the blood's pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis.

Type I-Distal RTA

Distal RTA (dRTA) is the classical form of RTA, being the first described. It has a number of causes which cause a common underlying problem, which is a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This leads to a failure to acidify the urine to a pH of less than 5.3 even if the blood is too acidic (ie there's systemic acidemia), and consequently there's a tendency towards acidemia. This leads to the clinical features of dRTA; in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described.
The symptoms and sequelae of dRTA are variable and ranging from being completely asymptomatic, through loin pain and hematuria from kidney stones to failure to thrive and severe rickets in childhood forms as well as possible renal failure and even death.
Interestingly, dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens' A Christmas Carol.

Causes

Autoimmune disease. Classically Sjögren's syndrome, but it's also associated with systemic lupus erythematosus, rheumatoid arthritis and even hypergammaglobulinemia. Hypokalaemia is often severe in these cases.

Hereditary causes include mutations of Band 3 the basolateral bicarbonate transporter of the intercalated cell, which may transmit in an autosomal dominant fashion in western European cases, or in an autosomal recessive fashion in South East Asian cases. The South East Asian cases are associated with more severe hypokaemia. Other Hereditary causes include mutations of subunits of the apical proton pump vH⁺-ATPase, which transmit in an autosomal recessive fashion, and may be associated with sensorineural deafness.

Liver cirrhosis.

Nephrocalcinosis. While it's a consequence of dRTA, it can also be a cause; related to calcium-induced damage of the cortical collecting duct.

Renal transplantation.

Sickle cell anemia.

Toxins, including ifosfamide, toluene, lithium carbonate and amphotericin B.

Chronic urinary tract obstruction.

Treatment

This is relatively straightforward. It involves correction of the acidemia with oral sodium bicarbonate or sodium citrate. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with potassium citrate tablets which not only replace potassium but also inhibit calcium excretion and thus exacerbate stone disease as sodium bicarbonate or citrate may do.

Type 2-Proximal RTA

Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify 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 generalised dysfunction of the proximal tubular cells called Fanconi's syndrome where there's also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria. The principal feature of Fanconi's syndrome is bone demineralisation due to phosphate wasting.

Causes

Familial disorders

Cystinosis

Galactosemia

Glycogen storage disease (type I)

Hereditary fructose intolerance

Lowe's syndrome

Tyrosinemia

Wilson's disease Acquired disorders

Amyloidosis

Multiple myeloma

Paroxysmal nocturnal hemoglobinuria

Toxins, such as HAART, ifosfamide, lead, and cadmium

Treatment

Again this depends on oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate diuresis. The amount of bicarbonate given may have to be very large, to stay ahead of the urinary losses. Correction with oral bicarbonate may exacerbate urinary potassium losses and precipitate hypokalemia.As with dRTA, reversal of the chronic acidosis should reverse bone demineralisation.

Type 3 RTA

This was previously used to designate a rare and transient mixed dRTA and pRTA of uncertain aetiology. Now it's used to describe a genetic defect in type 2 carbonic anhydrase (CA2), which is found in both the proximal and distal tubular cells, as well in bone. As a result it causes;

proximal renal tubular acidosis

distal renal tubular acidosis

osteopetrosis

cerebral calcification and subsequent mental impairment; It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb 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 4 RTA (Hypoaldosteronism)

Type 4 RTA isn't actually a tubular disorder at all, and nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it's associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in distal tubular ammonium excretion, which is secondary to hypoaldosteronism. Its cardinal feature is hyperkalemia, and measured urinary acidification is normal.

Causes

Aldosterone deficiency-Primary (rare)

Primary adrenal insufficiency

Congenital adrenal hyperplasia

Aldosterone synthase deficiency

Hyporeninemic hypoaldosteronism (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction)

Renal dysfunction-most commonly diabetic nephropathy

HIV infection

ACE inhibitors

NSAIDs

Cyclosporine

Aldosterone resistance

Drugs (Amiloride, Spironolactone,Trimethoprim, Pentamidine)

Pseudohypoaldosteronism

Treatment

Aldosterone deficiency should be treated with a mineralocorticoid (such as fludrocortisone), as well as possibly a glucocorticoid for cortisol deficiency, if present.

Hyporeninemic hypoaldosteronism is ammenable to fludrocortisone treatment,Further Information

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