Renal Handling of Glucose, Water, Salt & H⁺ – From the Proximal Tubule to the DCT

ONLY site of glucose re-absorption → if glucose passes the PCT it will appear in urine.
- Mechanism = secondary active cotransport (SGLT)
- Na^+ follows its electro-chemical gradient INTO the cell.
- Glucose or amino acids are dragged in AGAINST their gradient.
- Energetic cost is paid by the basolateral Na^+/K^+-ATPase.
  - Reaction:
Amino-acid re-absorption uses an identical Na⁺-amino-acid cotransporter.
Minor—but relevant—PCT re-absorptions
- ~65 % of filtered H_2O
- Electrolytes (Cl⁻, K^+, HCO_3^-)

Two limbs separated by a hair-pin turn
- Descending limb (thin) – permeable to H_2O, virtually impermeable to solute.
- Ascending limb (thick > thin) – impermeable to H_2O, rich in NaCl transporters.
Net purpose: create a counter-current multiplier that
- Reclaims the MAJORITY of remaining water (≈ 25 % of the filtered load).
- Recovers large amounts of NaCl (≈ 25 %).

Osmosis = diffusion of water from high to low water concentration (or low to high solute concentration) across a semi-permeable membrane.
Hyper- vs. hypo-tonic arms in a U-shaped glass example
- When solute cannot cross, water moves instead to equalise concentrations.
Charged/large species (e.g.
Na^+, Cl^-, glucose) require transporters.
H_2O can cross phospholipid bilayers directly (and faster via aquaporins).

Descending limb
- Environment outside the limb becomes progressively hyper-osmotic (high NaCl).
- Water diffuses OUT all along the descent → tubular fluid volume decreases, osmolarity rises.
- Point “A” (entry) has most water; point “E” (deepest spot) has least water left.
Ascending limb
- NaCl exits the filtrate through apical NKCC and other transporters; H_2O remains trapped.
- Highest luminal NaCl concentration = deepest segment (label “C” in narrative) → diffusion/active transport maximal there.
- As fluid ascends, NaCl load and osmolarity fall (by the time it reaches “A”/cortex it is hypo-osmotic).
Relationship between limbs
- Salt leaving the ascending limb raises interstitial osmolarity → drives still more water re-absorption from the descending limb (counter-current multiplier).

Normal blood glucose (~100\,mg/dL) → no glucose reaches the Loop.
Hyperglycaemia (e.g. 600\,mg/dL)
- PCT transporters saturated → excess glucose spills into the Loop.
- Extra solute ↑ tubular osmolarity → slows osmosis, so more water stays in tubular fluid.
- Result = larger urine volume (polyuria) and volume depletion → compensatory thirst (polydipsia).
Vocabulary
- Polyuria = excessive urination.
- Polydipsia = excessive thirst.
- Osmotic diuresis = diuresis driven by unreabsorbed solute (glucose).

Type 1
- Auto-immune destruction of pancreatic \beta-cells → no insulin production → absolute insulin requirement.
Type 2
- Insulin still produced, but peripheral insulin resistance develops (often lifestyle related).
Both types → risk of hyper-glycaemia, glycosuria, osmotic diuresis, dehydration.

Fine-tunes solute content; one highlighted function = acid–base regulation.
Basolateral cornerstone = Na^+/K^+-ATPase (uses ATP) establishing: high k {in}, high Na {out}
Step-wise H⁺ handling
1. Basolateral K^+/H^+ antiporter
- K^+ exits down its gradient, H^+ enters cell.
- Net effect on charge = 0 (both +1) → maintains membrane potential.
- Blood pH rises (less acid).
1. Apical Na^+/H^+ antiporter
- Na^+ enters cell (favoured by low [Na⁺] due to Na⁺/K⁺ pump), H^+ ejected into tubular fluid.
- Again electroneutral exchange.
Outcome: acid is transferred from blood → cell → filtrate without killing the cell or spending extra ATP (only basal pump consumes ATP).

Water reclaimed before DCT ≈ >90\% of filtered load.
Typical blood glucose threshold for saturation (renal Tm) ≈ \sim200\,mg/dL; values above → glucosuria.
Counter-current multiplier creates interstitial osmolarity in medulla up to \sim1200\,mOsm/L.

Same Na⁺ gradient generated by one ubiquitous pump (Na⁺/K⁺-ATPase) drives
- Glucose & amino acid retrieval (PCT)
- Massive salt reclamation (TAL of Loop)
- Acid secretion (DCT)
Charged/large solutes dictate where osmosis can/cannot occur → underpinning for how diabetes alters urine output.
Real-world relevance: understanding why diabetic patients present with dehydration, why loop diuretics target NKCC, and why kidney maintains pH homeostasis.