Renal Tubular Acidosis: types and pathology
Renal tubular acidosis (RTA) is a normal anion gap (hyperchloremic) metabolic acidosis in a patient with normal or almost normal renal function.
Patients with uremic acidosis (metabolic acidosis due to renal failure) have a decreased glomerular filtration rate (increased serum creatinine) and increased anion gap metabolic acidosis. Patients with renal tubular acidosis have relatively normal glomerular filtration rates and normal anion gap metabolic acidosis.
Types of RTA
Type 1-Distal RTA
Type 2-Proximal RTA
Type 3-Mixed RTA (a combination of 1 and 2)
Type 4-Hyperkalemic RTA
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Type 1-Distal RTA
Pathophysiology
The α-intercalated cells of the distal tubule are unable to secrete H+. It causes reduced intracellular production of HCO3- → reduced concentration of HCO3- in the blood → normal anion gap metabolic acidosis. It is hyperchloremic metabolic acidosis.
Chronic metabolic acidosis causes bones to release calcium carbonate and calcium phosphate in the blood as buffers (bone is a reservoir for the buffer). It increases free calcium in the blood, and it is excreted in the urine. The hypercalciuria with high urine pH is a recipe for calcium phosphate precipitation and stone formation. Nephrocalcinosis and renal stones are seen in DTA cases, sometimes patients present with nephrolithiasis.
Increased bone resorption causes reduced bone density and osteopenia.
Type 2-Proximal RTA
Pathophysiology
Defect in proximal convoluted tubular bicarbonate reabsorption → Increased excretion of HCO3- in urine → metabolic acidosis (hyperchloremic and normal anion gap acidosis.
Urine is acidified by intercalated cells in collecting tubule and urinary pH is < 5.5 ( >5.5 in beginning and less than 5.5 later when compensatory acidification starts).
Distal convoluted tubule and collecting duct cells secrete K+ and H+ to maintain ion equilibrium which causes hypokalemia. Hypokalemia in proximal RTA worsens with alkali therapy.
Type 2 RTA has two types -
Isolated – HCO3- reabsorption is defective
Generalized (Fanconi Syndrome)- total PCT shutdown, nothing is reabsorbed by PCT cells. It is also associated with hypophosphatemic rickets (phosphate is not reabsorbed, and phosphaturia causes vitamin D resistant rickets)
Type 3-Mixed RTA
Mixed RTA is a combination of Type 1 and Type 2 RTA.
It is a rare disorder and mostly affects children of Arabic, North African and middle eastern descent.
There is a defect in bicarbonate reabsorption. It is due to carbonic anhydrase type 2 deficiency.
It is also known as a marble brain disease.
Clinical features
- Sign and symptoms of Type 1 and Type 2 RTA
- Osteopetrosis
- Cerebral calcification
- Mental Retardation
Type 4-Hyperkalemic RTA
Pathophysiology
Aldosterone deficiency or resistance → impaired function of epithelial sodium channels at distal convoluted tubule, and hydrogen/ potassium pump at collecting duct → increased potassium and hydrogen in blood → hyperkalemia and metabolic acidosis.
Hyperkalemia → potassium ion shifts hydrogen ion out of the proximal tubule cells → PCT cells have no hydrogen ions → PCT cells are unable to synthesize NH4+ → decreased NH4+ excretion in urine (NH4+ is major urinary buffer).
Revision for today Renal cell carcinoma (RCC) - Creative Med Doses.
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