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PY7.1-9 | Renal Physiology — Part 3

Renal Regulation of Acid-Base Balance

Normal blood pH is 7.35–7.45. The kidneys are the only organ that can permanently eliminate acid from the body (the lungs can only adjust CO₂ — a volatile acid). The kidney handles approximately 50–100 mEq of fixed acid per day, produced from protein catabolism.

Three renal mechanisms for acid excretion:

1. Bicarbonate reabsorption (PCT, 85%):
Filtered HCO₃⁻ cannot be directly reabsorbed — it must first be converted. In the PCT:
- H⁺ secreted via NHE3 combines with HCO₃⁻ in the tubular lumen → H₂CO₃ → CO₂ + H₂O (catalysed by carbonic anhydrase IV on brush border)
- CO₂ diffuses into cell → combines with H₂O → H₂CO₃ (catalysed by carbonic anhydrase II intracellularly) → H⁺ + HCO₃⁻
- HCO₃⁻ exits to blood via Na⁺-HCO₃⁻ co-transporter; H⁺ is re-secreted
- Net effect: Secreted H⁺ is recycled — no acid is actually excreted, but HCO₃⁻ is returned to blood

2. Titratable acidity (phosphate buffer):
Filtered HPO₄²⁻ (dibasic phosphate) accepts a secreted H⁺ → H₂PO₄⁻ (monobasic) → excreted in urine. This is 'titratable' because you need to add base to titrate it back to pH 7.4.

3. Ammonium excretion (most important at high acid loads):
In tubular cells: Glutamine (from blood) → glutamate + NH₄⁺ (ammonium). NH₄⁺ is secreted into the tubular lumen (substitutes for H⁺ on NHE3 in PCT, diffuses as NH₃ then traps H⁺ in collecting duct). Can increase 10-fold in chronic acidosis.

Clinical connection: In our opening case patient with CKD (eGFR 18), the kidneys have lost the mass to secrete sufficient H⁺ → metabolic acidosis (low HCO₃⁻, low pH). Treatment: oral sodium bicarbonate supplementation.

Micturition: The Voiding Reflex

The bladder has two functions: storage (at low pressure, up to ~400 mL) and voiding (complete, coordinated emptying). These require opposite actions of detrusor muscle and urethral sphincters — coordinated by the pontine micturition centre (PMC) in the brainstem.

Bladder wall layers relevant to function:
- Detrusor muscle: Smooth muscle, contracts during voiding; controlled by M3 muscarinic receptors (parasympathetic)
- Internal urethral sphincter: Smooth muscle at bladder neck; closed by sympathetic (α1); absent in females (anatomical difference)
- External urethral sphincter: Skeletal muscle; under voluntary control via pudendal nerve (S2–S4)

Filling phase (storage):
As bladder fills, stretch receptors send signals via pelvic nerve to S2–S4. The sensation of fullness is perceived at ~150 mL, urgency at ~400 mL.
Sympathetic (T11–L2 via hypogastric nerve): β3 → relaxes detrusor; α1 → contracts internal sphincter. External sphincter: voluntarily contracted (pudendal).

Voiding phase:
When social circumstances allow, higher centres permit voiding:
- PMC activates sacral parasympathetics → M3 receptor → detrusor contracts
- PMC simultaneously inhibits pudendal nerve → external sphincter relaxes (Onuf's nucleus)
- Sympathetic reflexly inhibited → internal sphincter relaxes
- Coordinated: detrusor contracts + sphincters relax = voiding

Clinical relevance:
- Detrusor overactivity (uninhibited contractions) → urgency incontinence → treat with antimuscarinics (oxybutynin) or β3 agonists (mirabegron)
- Benign prostatic hyperplasia (BPH): α1 blockade (tamsulosin) relaxes internal sphincter — improves flow
- Spinal cord injury above S2: Loss of pontine control → reflex bladder (automatic voiding with no voluntary control)

Renal Function Tests & Clearance Concept (PY7.6, PY7.9)

Clearance is the volume of plasma completely cleared of a substance per minute:

C = (U × V) ÷ P
where U = urine concentration, V = urine flow rate (mL/min), P = plasma concentration

Inulin clearance = GFR (125 mL/min)
Inulin is freely filtered, neither reabsorbed nor secreted. Its clearance perfectly reflects GFR. (Gold standard but requires infusion — impractical clinically.)

Creatinine clearance ≈ GFR (slightly overestimates due to tubular secretion):
Used clinically. Collected over 24 h or estimated from serum creatinine (Cockcroft-Gault, MDRD, CKD-EPI formulas).

PAH clearance ≈ Renal Plasma Flow (625 mL/min):
PAH is filtered + maximally secreted → nearly 100% extracted in one pass → clearance = effective RPF. Renal blood flow = RPF ÷ (1 − haematocrit).

Interpreting tests in our patient (creatinine 3.4 mg/dL, eGFR 18):
- Stage G5 CKD (eGFR < 15 is kidney failure; 15–29 is G4 severely decreased)
- BUN (blood urea nitrogen): elevated (uraemia) — urea is freely filtered but 40–50% passively reabsorbed. BUN/creatinine ratio > 20 suggests pre-renal cause; normal ratio suggests intrinsic renal.
- Urinalysis: 3+ protein = nephrotic range (> 3.5 g/day) — suggests glomerular disease. Casts: granular and waxy casts suggest CKD; RBC casts suggest glomerulonephritis.