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+
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