SEARCH RESULTS FOR: type-ii-proximal-renal-tubular-acidosis-pathogenesis-and-laboratory-findings

type-ii-proximal-renal-tubular-acidosis-pathogenesis-and-laboratory-findings

Type II/Proximal Renal Tubular Acidosis: Pathogenesis and Laboratory Findings Authors: Wazaira Khan* Reviewers: Huneza Nadeem, Ran (Marissa) Zhang, Julian Midgley* * MD at time of publication Overview of bicarbonate reabsorption in the proximal tubule (PT): Serum bicarbonate (HCO3-) is filtered by the glomerulus and enters PT lumen H+ ATPase and sodium- hydrogen exchanger 3 (NHE3) on luminal surface of PT cell secrete H+ into PT lumen H+ combines with HCO3- in PT lumen to form carbonic acid (H2CO3) H2CO3 is broken down to H2O and CO2 by luminal membrane carbonic anhydrase 4 CO2 diffuses into PT cell CO2 reacts with H2O to form H2CO3 in PT cell, catalyzed by cytosolic carbonic anhydrase 2 H2CO3 rapidly breaks down intracellularly to form HCO3- and H+ HCO3- is reabsorbed into plasma by sodium bicarbonate transporter (NBCE1) on basolateral surface of PT cell HCO3- is available for use to buffer plasma H+ H+ is available intracellularly for use by H+ ATPase and NHE3 exchanger Mutation encoding NHE3 exchanger ↓ H+ secretion into PT lumen Galactosemia, Wilson disease, cystinosis, tyrosinemia, glycogen storage disorders Dent disease, Lowe syndrome Infiltrative disorders e.g., amyloidosis, multiple myeloma, monoclonal gammopathies Drugs e.g., tenofivir, ifosfamide, cisplatin Carbonic anhydrase inhibitors ↓ H2CO3 breakdown to H2O and CO2 Mutation encoding CAII enzyme, carbonic anhydrase inhibitors ↓ H2CO3 production in PT lumen ↓ CO2 diffusion into PT cell ↓ H2CO3 production in PT cell ↓ HCO3- production in PT cell ↓ HCO3- reabsorption by PT cell into plasma Type II/Proximal Renal Tubular Acidosis (RTA) Defective HCO3- reabsorption in proximal tubule Normal anion gap metabolic acidosis (NAGMA) See NAGMA slide Accumulation of toxic metabolites systemically, including in the PT Disruption of endocytosis and intracellular transport systemically, including in the PT Accumulation of light chain/amyloid deposits in PT Interfere with PT’s ability to reabsorb ions/molecules • • • • Fanconi Syndrome: generalized PT dysfunction Defective tubular reabsorption of other ions/molecules to varying degrees, including phosphate, glucose, sodium and amino acids Tubular proteinuria Phosphaturia Glucosuria ↑ Na+ secretionàhypovolemia Mutation encoding NBCE1 transporter ↑ HCO3- delivery to distal nephron K+ in distal nephron lumen binds to HCO3- K+ is lost through osmotic diuresis Hypokalemia Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 24, 2022 on www.thecalgaryguide.com