lecture 6 (renal) Flashcards
(30 cards)
what are the multiple interlinked buffer systems the body has?
- phosphate
- plasma protein
- haemoglobin
- HCO3-
what does proton concentration change?
- the dissociation of buffers
what factors determine pH ?
- pCO2
- HCO3-
how is bicarbonate broken down?
- by carbonic anhydrase
- broken into h2o and co2
what is the Henderson hasselbalch equation?
pH = pK’ + log HCO3-/alpha pCO2
pK’ = neg log off dissociation constant of eqn
alpha = solubility of co2 in plasma
what causes changes in acid base balance?
- diet
- metabolism (produces both)
- egestion (bicarbonate loss in faeces)
what is the net result?
- addition of acid to body
- corrected by excretion or buffering
what is volatile acid?
- acid produced from carbon dioxide
- can be excreted as co2
what is non volatile acid?
- acid produced in body from other sources (not co2)
- not excreted as co2
what is non volatile acid produced during?
- exercise
- heart disease
- respiratory disease
- diabetes
- amino acid metabolism
- phosphate containing food
how much bicarbonate is reabsorbed along the nephron?
- 80% in proximal tubule
- mostly all bicarbonate reaching nephron is absorbed
what is the process of bicarbonate reabsorption at PCT?
- bicarbonate comes down in tubular fluid
- epithelial cells allow bicarbonate entry into the blood
- combines with protons coming from sodium-proton anti porter
- coverts to carbonic acid
- rapidly breaks down to co2 and h2o
- taken up across apical membrane
- recombine in cell back to bicarbonate
- protons released able to drive the reaction
- reabsorbed into blood stream by NBC1
- for each sodium ion, 3 bicarbonate ions are transported
what is the concentration of bicarbonate in the urine?
- 0% (all reabsorbed)
how is bicarbonate reabsorbed in the thick ascending limb?
- very similar to in PCT
- sodium bicarbonate transporter NBC1n at basolateral membrane
- NHE3 = sodium proton antiporter
how is bicarbonate reabsorbed in the distal tubule and CCD?
- alpha intercalated cells (acid secreting cells)
- undergoes conversion to co2 and h2o
- moved into cell through aquaporins
- proton and bicarbonate generated
- apical membrane = HKA (proton potassium atpase) and V-ATPase (proton adenosine triphosphate)
- basolateral membrane = AE1 (chloride bicarbonate antiporter
how is new bicarbonate formed (stage 1)?
- requires proton (H+) excretion
- co2 and h2o combining to form bicarbonate which is reabsorbed through AE1
how is new bicarbonate formed (stage 2)?
- ammonia production in PCT by breakdown of glutamine to oxoglutamate then 2 bicarbonate molecules taken into bloodstream to buffer acid
- ammonium ion excretion (converts with ions to form)
- been secreted into tubular fluid, in ASL its reabsorbed into interstitium
what occurs if ammonium isn’t excreted?
- combined and generates acid
- bound by bicarbonate
- so no net production of bicarbonate
what determines the renal acid excretion?
- NH4+ excretion rate
- titratable acid x excretion rate
- amount of HCO3- lost in urine
how is proton secretion regulated by acidosis?
- H+ conc gradient promotes movement from cell into tubular lumen
- causes conformational change in transport proteins (proton out cell favoured)
- number of transporters in membrane increases
- transcription and translation of transporter genes and mRNAs increases
how do hormones regulate the proton secretion by acidosis?
- Endothelin-1 increases number of NBC1 and NHE3 transporters in cell membrane
- cortisol = increases transcription of NBC1 and MHE3 genes
- angiotensin II = increases NHE3 activity, stimulates NH4+ production and secretion
- aldosterone = acts in distal regions of nephron, increase during acidosis to increase proton secretion
what is the role of parathyroid hormone?
- inhibits phosphate reabsorption in PCT
- more available for H+ buffering in distal nephron
what is the role of the renal ET system in control of urinary acid excretion?
- dietary acid stimulates renal and adrenal ET-1 production
- increases proximal tubule H+ secretion and distal nephron H+ secretion and bicarbonate reabsorption
- adrenal ET-1 increases aldosterone which stimulates distal nephron H+ secretion
how do Renal cells sense pH?
- Pyk2 and Erb1/2 tyrosine kinase
- acid sensing GPCRs
- soluble adenylyl cyclase
