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Define uremic acidosis
Renal tubular acidosis + failure to filter food-derived acids (phosphate, sulfate)
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T/F: Renal tubular acidoses (RTAs) result in increased anion gap
F – for every bicarb you lose, you pick up a chloride
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Fanconi’s Syndrome can result in what type of RTA?
Proximal RTA
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What is the general defect in proximal RTAs?
Defective bicarb reclamation
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Obstruction leading to urine reflux into the collecting duct can result in what type of RTA?
Distal RTA
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T/F: Defective bicarb generation can occur in the absence of a distal tubular defect
T – could be a problem with ammoniagenesis
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How does defective ammoniagenesis result in a RTA?
Ammonia acts as a H+ trap in the collecting duct; without it, H+ cannot be secreted and therefore HCO3- cannot be generated/reabsorbed
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How does hypoaldosteronism result in a RTA?
Decreased aldosterone → decreased ammonia production and bicarb generation by the collecting duct
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The luminal (urine) pH must be below [#] in order for the CD H+ pump to work
4.5-5
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T/F: RTAs are always associated with decreased renal function
F – they can be associated with normal renal function (GFR > 50 mL/min.)
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T/F: Uremic acidosis is always associated with decreased renal function
T – GFR is usually less than 20 mL/min.
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3 causes of proximal RTA (pRTA)
• Fanconi’s (generalized reabsorption defect) | • Defective basolateral Na+/HCO3- transporter | • Acetazolamide-induced defect in brush-border carbonic anhydrase
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T/F: Patients with pRTA can still generate new bicarb
T – collecting duct function is intact
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Why are pRTAs associated with mild hypokalmia?
• Decreased paracellular K+ reabsorption in PCT | • Increased Na+ reabsorption in CD → increased K+ secretion
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Which RTA affects bones, and how?
pRTA → demineralizing bone disease (rickets, osteomalacia) | size • Enhanced H+/Ca2+ exchange on bone surfaces | • Decreased Vit. D production by PCT size
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Pharmacological therapy for pRTAs
Potassium citrate (citrate can be metabolized to bicarb, so it increases both K+ and bicarb)
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dRTAs could be caused by genetic defects in which transporters?
• Basolateral HCO3-/Cl- exchanger | • Apical H+ ATPase or H+/K+ ATPase
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Classical dRTA: | • Urine pH | • Potassium status | • Rare or common? | • Urine NH4+
• High (> 6) | • Chronic hypokalemia | • Rare | • Low
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Which RTA is a risk factor for kidney stones, and why?
dRTA → kidney stones (CaHPO4) | size • Acidosis stimulates citrate reabsorption for PCT bicarb generation → increase in free urine Ca2+ because it isn’t solvated by citrate | • Increased urine pH favors crystal formation size
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Pharmacological therapy for dRTAs
Replenish bicarb and K+ | • Replace daily H+ generation (50-100 mEq)
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What is the cause of Type 4 dRTA?
Reduced Na+ transport by the CD principal cells
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What could cause reduced principal cell Na+ transport (in Type 4 dRTA)?
• Aldosterone deficiency | • Drastically decreased distal Na+ delivery to the collecting duct
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What could cause decreased Na+ delivery to the collecting duct (in Type 4 RTA)?
• Diabetes mellitus – poor JGA function | • ACE inhibition | • Angiotensin II receptor blockade
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Type 4 dRTA: | • Rare or common | • Potassium status | • Urine pH | • Urine NH4+ | • Treatment
• Common | • Hyperkalemia | • Low (< 5.5) | • Low | • Loop diuretics
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Why does hyperkalemia develop in Type 4 dRTA and sick collecting duct syndrome?
Decreased Na+ presentation to the principal cell → decreased Na+ ENaC reabsorption → decreased K+ ROMK1 secretion
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Sick collecting duct syndrome (dRTA): | • Rare or common | • Potassium status | • Urine pH | • Urine NH4+ | • Treatment
• Common | • Hyperkalemia | • Variable | • Low | • Bicarb
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How do chronic RTAs affect calcium status?
• Osteomalacia/rickets | • Nephrolithiasis (renal stones) | • Hypercalciuria | • Muscle weakness from decreased intracellular Ca2+ stores in skeletal muscle
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In uremic acidosis, the anion gap is [increased, decreased, or normal]
increased
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Increased anion gap in uremic acidosis results from poor filtration of [?] and [?]
sulfate and phosphate
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Uremic acidosis is associated with [high, low, or normal] bicarb
low
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Patients with a non-anion gap acidosis normally have [high, low, or normal] chloride
high
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T/F: Patients can have a combined uremic acidosis and RTA (hyperchloremic)
T – this is very common
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Uremic acidosis + RTA: | • Chloride level | • Anion gap
• High | • Increased
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Normal anion gap
10 mEq/L
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