Bicarbonate Flashcards
Is bicarbonate mainly an intracellular or extracellular anion ? What is its principal function ?
Bicarbonate is mainly an extracellular anion
Buffer buffer of ECF and blood
State the equation that guides bicarbonate-acid interactions in the body, describing each element of this equation.
CO2 +H2O ↔ H2CO3 ↔ H+ + HCO3-
- CO2 is regulated by the respiratory system
- CO2 is a volatile acid (can be eliminated by being blown off)
- H+ (non volatile acid) is added to the body by diet and metabolism
- HCO3- is regulated by the kidneys, replacing any used up bicarbonate (and lost in feces each day)
Describe, using a mathematical formula, the link between bicarbonate and pH.
pH ∝ (HCO3-) / (pCO2)
Based on the following equation:
CO2 +H2O ↔ H2CO3 ↔ H+ + HCO3-
What would happen upon an increase in CO2 (e.g. suboptimal respiration) ?
What would happen upon an increase in metabolic acidemia ?
Shifts it to the right, i.e. more HCO3- and H+
H+ being added to the body in a metabolic acidemia, so uses up bicarbonate. Hence bicarbonate falls so pCO2 has to fall.
Define minute ventilation. What would happen to pCO2 if minute ventilation decreased ? to HCO3- ?
Minute ventilation = tidal V x resp rate
If minute ventilation decreases, paCO2 will increase, so HCO3- will increase as well (latter in order to maintain pH)
What kind of pathology is present if HCO3- and pCO2 move in opposite directions ?
Mixed acid base pathology
Identify the main overall actions performed by the kidney.
• Bicarbonate filtration (at the glomerulus) • Bicarbonate reabsorption • Bicarbonate regeneration by: – Titratable acid excretion – Ammonium excretion
Which of titratable acid excretion, or ammonium excretion is the larger component of bicarbonate regeneration ? the more constant one ?
Titratable acid excretion is the more constant one
Ammonium excretion is the larger component (Accounts for 2/3, versus 1/3 for titratable acid excretion. Can increase in times of need such as metabolic acidemia)
Describe the change in pH along the tubule.
Starts at pH 7.4 at the beginning of PT. As fluid progresses along lumen, becomes more acidic.
pH 6.9 in thick descending limb
pH 4.5 in collecting tubules
What is the per minute rate of glomerular filtration in a normal individual ? daily rate ?
120-125 mL/min
180 L /day
What is the normal plasma concentration of bicarbonate ?
Normal plasma bicarbonate 24mmol/l
How much of bicarbonate is filtered at Bowman’s capsule ?
Freely filtered (all of it)
Is bicarbonate mainly reabsorbed or not ? If so, where ?
Vast majority is reabsorbed
- 85-90% of filtered bicarbonate is reabsorbed around the proximal convoluted tubule
- Remaining 10-15% of filtered bicarbonate is reabsorbed in DT and Collecting Tubules
Which processes of reabsorption are common to both sites of bicarbonate reabsorption (PT on the one hand, and DT and Collecting Tubule on the other) ?
- Apical membrane is impermeable to bicarbonate.
- Bicarbonate in the tubular lumen therefore combines with H+, which forms CO2 + H2O.
- CO2 is freely diffusable, gets into cell, combines with H20 and carbonic anydrase to form HCO3- + H+ (quickly thanks to enzyme)
- HCO3- then gets into blood whilst H+ gets back in tubular lumen
Describe the process of proximal reabsorption of bicarbonate (specific to PT).
- In brush border of PT, carbonic anhydrase helps conversion of HCO3- + H+ into CO2 + H2O
- CO2 diffuses into renal tubule cell, combines with water in a reaction catalysed by carbonic anhydrase to form HCO3- + H+
- H+ transported back out into tubular lumen, through secondary active transporter (H+ Na+ exchanger, uses diffusion of Na+ into cell down its concentration gradient to transport H+ out)
- Na+ K+ ATPase (2 K+ in, 3 Na+ out) on the basolateral membrane is the driver to keep cell empty of sodium to create this concentration gradient
- Na+ HCO3- cotransporter on basolateral membrane then combines 1 Na+ out and 3HCO3- out
Describe the process of distal reabsorption of bicarbonate (specific to DT/Collecting Tubule).
- Conversion of HCO3- + H+ into CO2 + H2O in tubular lumen (WITHOUT Carbonic Anhydrase, slower process)
- CO2 diffuses into renal tubule cell, combines with water in a reaction catalysed by carbonic anhydrase to form HCO3- + H+
- Distally in tubule, urine much more acidic, i.e. more H+ in tubular lumen, so going along much less steep concentration gradient (if it were to diffuse out of the cell back into tubular lumen) so using ATP (H+ ATPase).
- Bicarbonate transported into blood through HCO3- Cl- exchanger
Why is bicarbonate regeneration necessary ?
- Acid is continually produced
- Protons consume bicarbonate (buffering system)
- This bicarbonate must be regenerated
- Bicarbonate regeneration will raise (bicarb) in the renal vein to a level higher than in the artery.
Describe the process of titratable acid excretion.
-H+ ion inside the cell, transported out into tubular lumen through Na+ H+ exchanger (secondary active transport, enabled by Na+ K+ ATPase on basolateral membrane creating steep Na+ concentration gradient)
-Instead of binding with bicarbonate ion, H+ binds to non bicarbonate buffer, mainly phosphate
-Phosphate exists in two forms: monoprotic and diprotic forms. Upon combination with H+, monoprotic form converted into diprotic form, essentially trapping
H ion in the urine, so it cannot escape back.
-CO2 is being produced inside cell by normal metabolism and bicarbonate into blood, combining with H2O in a reaction catalysed by carbonic anhydrase to form H+ (to which the aforementioned happens), and HCO3-, which is transported out using Na+ HCO3- cotransporter.
How does phosphate get into the lumen, in titratable acid excretion ?
By filtration just like bicarbonate (and just like other non-bicarbonate buffers)
Phosphate in tubular lumen comes from diet (e.g. chocolate, pheasant)
State the equation for the combination of the monoprotic form of phosphate with H+.
H+ + HPO4(2-) → H2PO4-
How does different parts of the tubule affect the equation: H+ + HPO4(2-) → H2PO4-
At start of PT, pH 7.4, 80% monoprotic form
As progress through tubule into more acidic territory, more H+ so shifts equation to the right, increasing amount of diprotic form
Identify non-bicarbonate buffers in urine.
- Phosphate (main one)
- Urate
- Creatinine
- Beta-hydroxybutyrate (ketone produced in diabetic ketoacidosis)
Describe the process of ammonium excretion.
- Glutamine is produced by liver, gets to kidney via bloodstream
- In academia, increased production by liver, and take up by kidney increases
- Inside cell, glutamine metabolised into alpha ketoglutarate (AKG2-), with side product of ammonium ion which is excreted into tubular lumen via NH4+ Na+ exchanger (same exchanger as Na+ H+ exchanger)
- AKG2- + H+ (protons (and bicarbonate) obtained from reaction of CO2 with H2O catalysed by carbonic anhydrase) results in CO2 + H2O (or glucose)
- Bicarbonate is transported into blood via HCO3- Na+ cotransport (3 bicarbonates out and 1 Na+ out)
- Powerhouse still present to maintain low Na+ and high K+ inside the cell, which drives excretion of ammonium
Overall result of this process is regeneration of bicarbonate, and ammonium excretion.
Where in the kidney does ammonium excretion mainly occur ?
Mainly in PT