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Ammonia transport in renal
tubules
Akinchan Bhardwaj
INTRODUCTION
• Ammonia metabolism and transport is
predominant mechanism of acid- base balance
• Minimal amount through glomerular filtration
• Ammonia is produced by kidney and selectively
transported into urine or renal vein
• Excreted in urine as NH4+ with equimolar
formation of bicarbonate
• Ammonia metabolised by liver with consumption
of bicarbonate
AMMONIA: Chemistry
• 2 molecular forms: NH3 and NH4+ (MAJORITY
• In a buffer reaction between NH3 and NH4+
WITH PkA OF 9.15
• NH3 is a polar moleculewith limited lipid
permeability
• NH4+ and K+ similar biophysical properties so
NH4+ can be transported at K+ transport site
of various proteins
AMMONIA PRODUCTION
• Produced by amlmost all renal eithelia cells
but predominantly in PCT
• Primary substrate Glutamine
• Multiple pathways are present
• PDG ( phosphate dependent glutaminase):
inner mitochondrial membrane metabolises
glutamine to glutamate producing NH4+
AMMONIA TRANSPORT
SPECIFIC PROTEINS INVOLVED
• Phosphate dependent glutaminase
• Glutamate dehydrogenase
• Phosphoenol pyruvate carboxykinase
• Gamma glutamyl transpeptidase
• Na+/H+ exchanger type 3
• Potsssium channels
• Na-K-2Cl cotransporter
• Na-K-ATPase
• Aquaporins
• Carbonic anhydrase
• Rh glycoproteins
AMMONIA TRANSPORT
• Produced in proximal tubule transported to
lumen
• Preferential apical secretion by multiple factors:
– Increased luminla acidification which facilitates
trapping of secreted NH3 as NH4+
– NHE3 medicted Na+/NH4+ exchange
• PCT can also reabsorb ammonia
• Metabolic acidosis leads to net secretion of
ammonia rather than reabsorption
AMMONIA TRANSPORT
• TAL: reabsorbs luminal ammonia mainly
mediated by apical Na-K-2Cl co-transporter
• Some of the ammonia av=bsorbed by
medullary TAL recycled into thin descending
limb
• l/t Countercutrrent amplification of medullary
interstitial ammonia concentration.
• Ammonia secretion by collecting duct decides
majority of urinary ammonia content
• CD ammonia secretion involves parallel NH3 and
H+ transport
• Carbonic Anhydrase also has a role by supplying
H+ for secretion
• Presence or absence of luminal carbonic
anhydrase activity has an important impact on CD
ammonia secretion
• and IMCD
• Rh glycoprotein also plays a role in renal
ammonia excretion
• Rhcg is a specific ammonia transporter
expressed in DCT,CNT,ICT,CCD,OMCD
• Intercalated cell specific Rhcg deletion
decreases response to metabolic acidosis
• Rhbg is ammonia specific transporter similar
to Rhcg but expressed basolaterally

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Ammonia transport in renal tubules

  • 1. Ammonia transport in renal tubules Akinchan Bhardwaj
  • 2. INTRODUCTION • Ammonia metabolism and transport is predominant mechanism of acid- base balance • Minimal amount through glomerular filtration • Ammonia is produced by kidney and selectively transported into urine or renal vein • Excreted in urine as NH4+ with equimolar formation of bicarbonate • Ammonia metabolised by liver with consumption of bicarbonate
  • 3. AMMONIA: Chemistry • 2 molecular forms: NH3 and NH4+ (MAJORITY • In a buffer reaction between NH3 and NH4+ WITH PkA OF 9.15 • NH3 is a polar moleculewith limited lipid permeability • NH4+ and K+ similar biophysical properties so NH4+ can be transported at K+ transport site of various proteins
  • 4.
  • 5. AMMONIA PRODUCTION • Produced by amlmost all renal eithelia cells but predominantly in PCT • Primary substrate Glutamine • Multiple pathways are present • PDG ( phosphate dependent glutaminase): inner mitochondrial membrane metabolises glutamine to glutamate producing NH4+
  • 6.
  • 8. SPECIFIC PROTEINS INVOLVED • Phosphate dependent glutaminase • Glutamate dehydrogenase • Phosphoenol pyruvate carboxykinase • Gamma glutamyl transpeptidase • Na+/H+ exchanger type 3 • Potsssium channels • Na-K-2Cl cotransporter • Na-K-ATPase • Aquaporins • Carbonic anhydrase • Rh glycoproteins
  • 9. AMMONIA TRANSPORT • Produced in proximal tubule transported to lumen • Preferential apical secretion by multiple factors: – Increased luminla acidification which facilitates trapping of secreted NH3 as NH4+ – NHE3 medicted Na+/NH4+ exchange • PCT can also reabsorb ammonia • Metabolic acidosis leads to net secretion of ammonia rather than reabsorption
  • 10. AMMONIA TRANSPORT • TAL: reabsorbs luminal ammonia mainly mediated by apical Na-K-2Cl co-transporter • Some of the ammonia av=bsorbed by medullary TAL recycled into thin descending limb • l/t Countercutrrent amplification of medullary interstitial ammonia concentration.
  • 11. • Ammonia secretion by collecting duct decides majority of urinary ammonia content • CD ammonia secretion involves parallel NH3 and H+ transport • Carbonic Anhydrase also has a role by supplying H+ for secretion • Presence or absence of luminal carbonic anhydrase activity has an important impact on CD ammonia secretion • and IMCD
  • 12. • Rh glycoprotein also plays a role in renal ammonia excretion • Rhcg is a specific ammonia transporter expressed in DCT,CNT,ICT,CCD,OMCD • Intercalated cell specific Rhcg deletion decreases response to metabolic acidosis • Rhbg is ammonia specific transporter similar to Rhcg but expressed basolaterally