Renal Tubular Acidosis

My Nephrology attending told me that even though RTA's are not very common in the population, they are a favorite topic on the boards. 

Type 1 Distal RTA

Pathology-a defective H/K pump in the distal tubule. As a result, the kidneys fail to secrete hydrogen into the urine and they fail to reabsorb potassium back into the lumen.

Clinical Presentation-Since the kidneys are unable to secrete hydrogen into the urine, there will be acidemia of the blood and the urine will be alkaline pH > 5.4. Since the kidneys cannot reabsorb potassium from the urine, there will be hypokalemia. Nephroliathasis can be a problem because stones will form in more alkaline urine and acidemia of the blood will cause bone resorption. 

Causes-Think autoimmune disorders (Sjogren’s, RA, SLE). Drugs (ifosfamide, ampho B, lithium), sickle cell anemia, hypercalciuria, hyperglobulinemia, cirrhosis, obstructive uropathy, or renal transplant.

Diagnosis-Acid load the body with ammonium chloride. Even though you have put acid in the body, the urine will remain alkaline because the kidneys cannot excrete the excess hydrogen. There will be a positive urine ion gap. A positive urine ion gap can happen 1 of 2 ways. 

UAG = (Na+K) - (CL) = Unmeasured anions-Unmeasured cations

1. If the Unmeasured cations are = 0 then you will get a positive UAG. NH4+ is the form of acid that the kidney secretes. If it is unable to secrete the acid, as is the case in RTA type 1, then you will be a 0 for the unmeasured cation and thus, a positive UAG. 

2. If the Unmeasured urine anion is extremely elevated 

Treatment-Oral Bicarbonate. This will treat the acidemia and also help prevent nephrolithiasis by making the urine more alkaline. 

Type 2 Proximal RTA

Pathology-The kidneys have defective HCO3 reabsorption. 

Clinical Presentation-The urinary pH will be <5.4. When I was revisiting this, I wondered why the urine wouldn't be alkaline if the kidneys were unable to reabsorb bicarbonate. The reason is that the defect is in the proximal part of the tubule. The distal part of the tubule still works well so the kidneys are able to acidify the urine and will correct the acid base balance in the end. There will also be hypokalemia because the early acidemia of the urine will cause overactivation of the H/K pumps and will secrete out more K into the urine. RTA type 2 may also cause rickets or osteomalacia. This is because a defect in the proximal tubule causes loss of phosphate into the urine. 

Causes- In adults think multiple myeloma or certain drugs. The light chains in multiple myeloma are resistant to degradation in the proximal tubular cells and accumulate there to cause impairment. Other things to consider are primary causes such as familial disorders (cystinosis, Wilson’s, glycogen storage disease type I. Secondary causes include multiple myeloma, amyloidosis, drugs (ifosfamide, carbonic anhydrase inhibitors), heavy metals (lead, mercury, copper). It helps me to remember this by thinking about the heavy metals getting flushed into the renal tubules and damaging the first part that they come into contact with which is the proximal tubule.  

Note-Fanconi's Syndrome is a disorder of the proximal tubule and but more generalized than RTA type 2 defect of diminished HCO3 reabsorption. In Fanconi's syndrome, the kidneys lose almost everything that is suppose to be reabsorbed in the proximal tubule so you will see glucosuria, phosphaturia, uricosuria, aminoaciduria, and tubular proteinuria. Most Fanconi's syndrome cases will include a type 2 RTA. 

Diagnosis-measure HCO3 in the urine

Treatment-Thiazides, oral bicarbonate and vitamin D supplements may be needed to treat underlying bone disease. 

Type 4 RTA AKA Hyperkalemic RTA

Pathology-cause is that the kidneys have a generalized transport abnormality of the distal tubule. This form is distinguished from classical distal RTA and proximal RTA because it results in high levels of potassium in the blood instead of low levels. It can occur when blood levels of the hormone aldosterone are low or when the kidneys do not respond to Aldosterone. Aldosterone directs the kidneys to reabsorb Na and excrete K. 

Clinical Presentation-Hyperkalemia and symptoms such as low BP, salt craving or DM

Causes-Due to either aldosterone deficiency (diabetic nephropathy) or tubular resistance to the action of aldosterone (chronic tubulointersitial disease or potassium-sparing diuretics). 

Diagnosis-Low serum aldosterone 

Treatment-Furosemide, mineralcorticoid replacement such as Fludrocortisone.