Physiological Basis: A number of processes take place in
the proximal and distal kidney tubules which relate to acid-base and electrolyte
balance. There are three ions of primary interest in RTA:
Bicarbonate: 80-85 percent of HCO3- is reabsorbed in the proximal convoluted tubule and another 5-10% is absorbed in the proximal straight tubule and loop of Henle. Carbonic anhydrase located in the proximal tubule is important for HCO3- reabsorbtion.
Ammonium: NH3 is produced in the PCT by metabolism of glutamine to alpha-ketoglutarate and is secreted into the lumen as NH4+. About 70% is reabsorbed in the thick ascending loop of Henle in a process known as medullary cycling. Here it is in equalibrium with NH3 and H+. The NH3 can diffuse into medullary collecting ducts. Trapping takes place here when a proton converts it to NH4+ which cannot diffuse back out of the lumen and must be excreted.
Protons: Protons are secreted is the collecting duct by an electrogenic H+/ATPase. For each proton secreted, an HCO3- is transferred to circulation by the chloride/bicarbonate exchanger located on the basolateral membrane here.
Proximal (Type II) RTA: Associated with loss of bicarbonate (failure to reabsorb HCO3-), or decreased ammonium excretion into the tubule lumen. This type of RTA is often part of Fanconi syndrome (in which there is also proximal tubule loss of glucose, calcium, phosphate, other electrolytes, and organic acids). Type II is clinically associated with failure to thrive. At serum HCO3- levels less than 15 mmol, HCO3- is reabsorbed efficiently. Below this level, urine pH will be below 5.5 indicating efficient reabsorbtion of HCO3-, otherwise urine pH is greater than 6 in the presence of a metabolic acidosis. Inhibitors of carbonic anhydrase also cause Type II RTA.
Distal (Type I) RTA: There are four subdivisions within Type I RTA, all of which relate to difficulties in maintaining a secretory proton gradient in the distal portion of the tubule system. Incomplete dRTA is seen only when an acid load exceeds the proton excretion mechanism. dRTA responds better to oral alkali treatment than pRTA.
|Finding||Distal (I)||Proximal (II)||Type IV|
|Serum K||Normal to decreased||Normal to decreased||Increased|
|Urine pH during acidosis||> 6||< 6||< 6|
|Net acid excretion with
|Calcium excretion||Increased||Normal to increased||Normal (?)|
with normal serum HCO3
|< 5||> 15||< 15|
|(urine - blood) PCO2||Decreased||Normal||?|
|Daily alkali Tx (mEq/kg/day)||1-4||2-15||2-3|
|Requirement for K||no||increased||no|
Urine Acidification Tests: The short ammonium chloride loading test consists of measuring urine pH 6-8 hours after administration of 0.1g/kg of NH4Cl. Failure to acidify to a pH of less than 5.3 suggests dRTA (gradient-dependent, or problems with electrical gradient or membrane permeability). It will be less than 5.5 in Type II and IV, as well as rate-limited dRTA.
NaSO4 administration: The patient is made salt-avid by restriction or furosemide treatment and then given NaSO4. The sulfate is not resorbable, and a steep voltage gradient is created. Urine pH should be less than 5.5; if not, there is either a defect in proton pump function or distal Na+ reabsorbtion.
Fractional Excretion of HCO3- (FEHCO3): Urine pH is monitored as the patient is given HCO3 until a level of 30 mmol/L is reached. In pRTA, as soon as the threshold of 15 mmol/L is exceeded, the FEHCO3 will increase to 15%. In other patients, the FEHCO3 will remain about 3% indicating good reabsorbtion.
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