Pathophysiology
Summary
Renal tubular acidosis (RTA) represents a group of disorders characterized by non-anion gap metabolic acidosis due to defective renal tubular function. The principal forms include type 1 (distal), type 2 (proximal), and type 4 RTA. These conditions have implications on the body's acid-base balance, electrolyte levels, and ultimately, systemic metabolism.
Type 1 RTA is primarily caused by a dysfunctional H+ ATPase in α-intercalated cells of the collecting duct. This results in decreased secretion of H+ and NH4+, leading to a basic urine pH (> 5.5) and low urine ammonium. Patients often present with hypokalemia and may develop calcium phosphate kidney stones due to metabolic acidosis-triggered bone resorption and low urinary citrate levels. The condition is most commonly associated with autoimmune disorders in adults (Sjögren’s, RA) and hereditary causes in children. Hypercalcemia and drugs like amphotericin B and lithium can also induce type 1 RTA.
Type 2 RTA is marked by decreased bicarbonate reabsorption in the PCT and has the distinctive feature of being self-limiting. The urine is initially alkaline, but normalizes over time due to compensatory mechanisms in the distal kidney. Hypokalemia is also a frequent presentation, and the condition can be part of a broader disorder known as Fanconi syndrome, which is associated with generalized reabsorption defect in the PCT. Acetazolamide is a notable drug that can induce type 2 RTA by inhibiting carbonic anhydrase, thus preventing bicarbonate reabsorption.
Type 4 RTA is predominantly due to a deficiency of aldosterone, leading to hyperkalemia. Hyperkalemia inhibits ammonium production by in PCT, further aggravating metabolic acidosis and causing intracellular alkalosis. A distinguishing characteristic of type 4 RTA is the maintenance of a relatively normal urine pH, which is attributed to mechanisms for proton secretion independent of aldosterone. Factors contributing to this disorder include conditions resulting in reduced levels of renin or aldosterone, as well as medications like ACE inhibitors, heparin, and spironolactone.
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FAQs
Renal tubular acidosis (RTA) is a set of disorders characterized by normal anion gap metabolic acidosis due to dysfunctional renal tubules, resulting in the inability to acidify urine and subsequent metabolic acidosis. RTA can be categorized based on the specific renal tubule affected: type 1 involves the collecting duct, type 2 involves the proximal convoluted tubule, and type 4 is associated with aldosterone deficiency. All forms result in an imbalance of acid in the body due to inadequate renal acid secretion.
Type 1 RTA, also known as distal RTA, is commonly caused by autoimmune disorders like Sjogren syndrome and rheumatoid arthritis in adults, while hereditary factors are more prevalent in children. Certain medications such as amphotericin B and lithium can also induce this condition. Clinically, it presents with hypokalemia and metabolic acidosis. The urine is typically basic with a pH greater than 5.5, and there is a decreased secretion of hydrogen ions and ammonium. Additionally, patients may develop calcium phosphate kidney stones.
Type 2 RTA, or proximal RTA, is characterized by impaired bicarbonate reabsorption in the proximal convoluted tubule. This leads to excess bicarbonate secretion in the urine and results in non-anion gap metabolic acidosis. The urine pH is initially basic but eventually normalizes due to compensatory mechanisms in the distal nephron. Common causes include Fanconi syndrome and medications like acetazolamide, which inhibit carbonic anhydrase. Patients often present with hypokalemia.
Type 4 RTA is unique in that it is associated with hyperkalemia, typically due to a deficiency in aldosterone. This hyperkalemia inhibits ammonium production in the proximal tubule, leading to metabolic acidosis. Causes can range from conditions that lower renin levels to medications that inhibit aldosterone synthesis or function, such as ACE inhibitors, spironolactone, and heparin. Unlike other types, the urine pH in type 4 RTA is usually normal.
Intercalated cells in the renal tubules contain a proton pump known as H+ ATPase, which is responsible for secreting protons into the collecting duct lumen. These protons facilitate the conversion of ammonia to ammonium, aiding in acid secretion as NH4+. In type 1 RTA, this H+ ATPase becomes dysfunctional, leading to a decrease in proton and ammonium secretion, resulting in metabolic acidosis and a more basic urine pH.
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