Renal tubular acidosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]
Overview
Pathophysiology
Normal Physiology of Acid-Base balance
- Normally kidneys reabsorb the filtered bicarbonate and excrete acid to maintain acid-base balance.
- HCO3 reabsorption is facilitated by Na-H and proton pumps.
- Na-H reabsorbs about 80-90% of the filtered HCO3 at the proximal tubule.
- Proton pumps (H-ATPase and H-K ATPase) in the distal nephron reabsorbs remaining 10 percent of HCO3.
- There is no HCO3 in the final urine.
- Collecting tubules serve the function of excretion of acid.
- Hydrogen ions need a buffer to get excreted.
- The principal buffers in the urine are ammonia and phosphate.
- Acidosis stimulates ammonia production in renal tubules.
- While ammonia can freely diffuse across membranes, ammonium cannot.
- The secretion of hydrogen ions into the tubular lumen trap ammonia as ammonium which can easily flush out along with .
- Increased production of ammonium is required in cases of acidosis to maintain near-normal balance.
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Potassium
- Potassium is the most common electrolyte abnormality that can be noticed with renal tubular acidosis.
- It can be either hypokalemic renal tubular acidosis or hyperkalemic renal tubular acidosis.
- Almost all of the filtered potassium is reabsorbed passively in the proximal tubule and loop of Henle.
- The potassium excreted in the urine is derived from secretion into the tubular lumen by cells in the distal nephron.
- Distal potassium secretion is primarily influenced by two factors, both promote sodium reabsorption:
- Depending upon the site of the defect and the mechanism responsible for the various forms of RTA, can result in hypokalemia or hyperkalemia:
- Hypokalemia frequently develops in patients with distal RTA.
- Usually improves with alkali therapy in contrast to to hypokalemia in proximal RTA which is exacerbated by alkali therapy.
- Hyperkalemia occurs frequently with hypoaldosteronism (type 4 RTA) and in patients with other defects in distal nephron sodium reabsorption (voltage-dependent RTA).
Distal (type 1) RTA
- Type 1 renal tubular acidosis is characterized by impaired hydrogen ion secretion in the distal nephron.
- If left untreated, it results in progressive hydrogen ion retention leading to normal anion gap metabolic acidosis.
- Type 1 renal tubular acidosis results in hypokalemia.
- Impaired hydrogen ion secretion in patients with distal RTA can be caused by several defects:
- Decreased net activity of the proton pump.
- Increased hydrogen ion permeability of the luminal membrane.
Incomplete distal RTA
- Incomplete distal RTA is a variant in which patients cannot acidify their urine, resulting in a urine pH that is persistently 5.5 or higher.
- The low rate of citrate excretion and relatively high rate of ammonium excretion are believed to the inciting factor for a reduced intracellular pH within the cells of the proximal tubule .
- Persistent hypo-citraturia is a consistent feature of incomplete RTA.
Proximal RTA
- Proximal (type 2) renal tubular acidosis is characterized by a decrease in re-absorption of bicarbonate in the proximal tubule.
- Within proximal tubule cells, hydrogen ions and bicarbonate are generated from carbonic acid.
- Na-K-ATPase pump facilitates the movement of sodium down the electrochemical concentration gradient from the lumen into the cells.
- This concentration gradient drives hydrogen ions in the opposite direction which is counter balanced by bicarbonate ions via a sodium-bicarbonate cotransporter.
- The net effect of this process is that, for every hydrogen ion molecule secreted into the lumen, a bicarbonate molecule enters the peritubular capillary.
- Abnormalities of one or more of these proximal tubule transporters, pumps, or enzymes can impair sodium bicarbonate reabsorption and cause the bicarbonate wasting found in proximal renal tubular acidosis.
Type of RTA | Primary defect | Plasma HCO3 mEq/L | Urine pH | Plasma potassium | Urine anion gap | Urine calcium/creatinine ratio | Risk for nephrolithiasis |
---|---|---|---|---|---|---|---|
RTA type 1 | Impaired distal acidification | < 10 | >5.3 | Hypokalemic | Positive | ↑ | ↑ |
RTA Type 2 | Reduced proximal HCO3 reabsorption. | 12 to 20 | <5.3 | Hypokalemic | Negative | Normal | - |
RTA type 4 | Decreased aldosterone secretion
Aldosterone resistance |
>17 | Variable | Hyperkalemia | Positive | Normal | - |
Voltage-dependent RTA | Reduced sodium reabsorption | >17 | Variable | Hyperkalemia | Positive | Normal | - |