20B19: Exam Report

Explain how the kidney handles an acid load

51% of candidates passed this question.

This question required candidates to understand the renal response to an acid load. It was expected that candidates would answer with regard to recycling of bicarbonate in the proximal tubule, excretion of titratable acid via the phosphate buffer system and generation of ammonium and its role in acid secretion. Many candidates had a good understanding of the bicarbonate system but used this to explain the secretion of new acid.

14B12: Exam Report

Describe the role of the kidneys in the excretion of non-volatile acid.

27% of candidates passed this question.

This is a complex but essential area of physiology for intensive care practice. It was expected candidates would indicate that non-volatile acids are those not able to eliminated by the lungs (lactate, sulphate, phosphate and ketone bodies). The kidney plays a central role via bicarbonate (resorbing filtered bicarbonate and generating “new” bicarbonate = acid excretion). It was
expected candidates could detail the processes in various parts of the renal tubules and the role or urinary buffers (dibasic phosphate and ammonia).

While a number of candidates were able to provide some of the details of ion transports in the kidney, few showed understanding of the overarching concepts of the proximal bicarbonate reabsorption being necessary to allow the distal acid excretion.

H1v / 20B19 / 14B12: Describe the role of the kidneys in the excretion of non-volatile acid

Definition

Non-volatile acid: an acid not excreted by lungs

  • Fixed acid production = 1 mmol / kg / day
  • Due to incomplete metabolism of:
    • Carbohydrates → lactate → 1500 mmol/day
    • Protein → sulphate, phosphate → 55 mmol/day
    • Fat → ketones → 12 mmol/day
  • These acids require excretion by the kidneys for acid-base balance (~70 mmol/day)

NB: lactic acid is exempt because 1500mmol of lactic acid produced is oxidised by the liver to regenerate HCO3–

  • Kidney has 2 important roles in acid-base & excretion of fixed acids
    1. Reabsorb all filtered HCO3– (4320 mol/day)
    2. Excrete fixed acids (70 mmol/day)

1) HCO3- Reabsorption

  • Daily acid load cannot be excreted unless all filtered HCO3– is reabsorbed
  • Because both derived from H2CO3 dissociation
    • H2CO3 ⮂ H+ + HCO3–
  • Losing HCO3– is like gaining H+
  • HCO3– reabsorption
    • 80% PCT
    • 15% thick ascending LoH
    • Rest Type A intercalated cells of Collecting Duct
HCO3- Reabsorption
  • Plasma HCO3– = 24mmol/L
  • GFR = 180L/d
  • ∴Filtered HCO3– = 4320 mmol/day
  • HCO3– reabsorption is active

PCT

  • CA present on apical membrane & inside tubule cells
  • Catalyse: CO2 + H2O ⮂ H2CO­3 ⮂ H+ + HCO3–
  • HCO3– produced inside tubule cell is reabsorbed across BL membrane → peritubular caps
  • H+ crosses apical membrane → CO2 + H2O

∴H+ is not added to urine → forms H2O with CA enzyme on apical membrane

Transporters Required

  • Na/K/ATPase BL membrane to reabsorption Na+
  • Na/3HCO3– – symporter BL membrane to reabsorb HCO3–
  • Na/H antiporter apical membrane to secrete H+ (Bonus – reabsorbs Na+!)
Transporter

Thick Ascending LoH

  • Reabsorbs 15% HCO3– filtered
  • Similar to PCT

DCT/Collecting Ducts

Type A Intercalated Cells

  • Secrete H+ to form titratable acid & reabsorb HCO3–
  • Transporters
    • H/ATPase
    • H/K/ATPase (↑ with aldosterone)
    • Cl/HCO3– symporter
Type A Intercalated Cells

2) Fixed Acid Excretion

  • Requires new HCO3– to be formed
  • Difficult to excrete free H+ because its urine concentration is so low < 0.04mol/L even at the most acidic pH
  • Fixed acid = 70 mmol/day
  • 2 buffer system in URINE
    • AMMONIA → excretes 50 mol
    • PHOSPHATE → excretes 20 mol

Phosphate buffer system

  • H2PO4 (weak acid) ⮂ H+ + HPO42-
  • H2PO4– is the “titratable acid” & refers to the amount of NaOH required to titrate the urine to pH 7.4 (which must equal the amount of H+ mol in urine)
  • NH4+ is not part of titratable acidity. pKa 9.2
  • ∴ exists as NH4+ & does not dissociate in urine
  • ∴ doesn’t contribute to urinary pH (& ∴ not measured w titration)
  • NB: To measure, you need to measure urinary NH4+

Phosphate Buffer

  • = pKa 6.8
  • Occurs in late DCT & collecting duct
  • H+ secreted into tubule lumen & binds HPO42-
  • To reach min. tubule pH 4.4
Phosphate Buffer

Note on Phosphate

  • Plasma phosphate = 1 mmol/L
  • 90% free, rest bound to plasma proteins
  • GFR 180L / day ~160 mol /day filtered phosphate
  • ~90% reabsorbed
  • ∴ ~40 mol/day un-reabsorbed H2PO4– available for buffering

BUT

This system cannot be upregulated with ↑ acid load

  • At pH 7.4 80% base HPO42- and 20% weak acid H2PO4–
  • But as tubule fluid pH ↓, most is converted to acid H2PO4–

Ammonium Buffer = pKa 9

  • In PCT cells extract glutamine from GFR & peritubular capsule
  • Glutamine → 2NH4+ + 2HCO3–
  • Na/NH4 antiporter secretes NH4+ into tubule fluid
  • HCO3– diffuses into peritubular caps
  • NH4+ is not lipid soluble & trapped in tubule lumen → (excreted H+)
Ammonium Buffer

Thick Ascending Limb

  • 80% NH4+ reabsorbed
  • Na / K / 2Cl multiporter with NH4+ substituting for K+
  • Causes NH4+ to accumulate in interstitium of medulla
  • Its [ ] ↑ approaching papillar & some is secreted into Thin Desc. Limbs
  • This is ‘ammonium recycling’ & some trapped in medullary interstitium
Thick Ascending Limb

Collecting Ducts

  • NH4+ secretion
  • That which is reabsorbed in Thick Asc. Limb is put back into tubule & secreted

Overall : new HCO3– reabsorbed

Collecting Ducts

Other buffers contributing to titratable acidity (but not that significant):

  • Creatinine
    • pKa 4.9 → at pH 4.4 in urine can contribute to titratable acidity 
  • B hydroxybutarate & acetoacetate
    • pKa 4.5 → ketoacids appear in urine during DKA. Act as buffers during severe metabolic acidosis (because the H+ will only bind with them at low urinary pH due to their pKa)