Proximal convoluted tubule

Tubulus contortus proximalis

Also known as: PCT, proximal tubule, pars convoluta

The first, longest (≈14 mm) segment of the renal tubule, lined by brush-bordered cuboidal cells rich in mitochondria, which isosmotically reabsorbs ≈65–67% of filtered Na⁺ and water and nearly all filtered glucose, amino acids and most bicarbonate.

Show on body map Nephron — Juxtamedullary

Overview

Length≈14 mm

Na⁺/water reabsorbed≈65–67%

Glucose renal threshold≈180–200 mg/dL

Tubular fluid osmolality≈300 mOsm/kg (isosmotic)

The PCT begins at the urinary pole of Bowman capsule, coils near its own glomerulus in the cortex (pars convoluta) and continues as the straight part (pars recta) descending in a medullary ray into the outer medulla. Its segments S1, S2 and S3 differ progressively in transporter content.

Reabsorption is driven by the basolateral Na⁺/K⁺-ATPase. In the early PCT, Na⁺ enters with glucose (SGLT2), amino acids, phosphate (NaPi-IIa) and lactate, and in exchange for H⁺ (NHE3); secreted H⁺ combines with filtered HCO₃⁻ (carbonic anhydrase IV/II) so ≈80–90% of filtered HCO₃⁻ is reclaimed. Cl⁻ is reabsorbed later, as its luminal concentration rises, via paracellular and Cl⁻/anion exchange routes. Water follows osmotically through AQP1 and between cells, so tubular fluid stays isosmotic (≈300 mOsm/kg). Filtered small proteins and albumin are endocytosed (megalin–cubilin) and degraded. About 65% of K⁺ and Ca²⁺ and ≈50% of urea are reabsorbed passively.

Secretion: organic anions (PAH, urate, penicillins, loop and thiazide diuretics, methotrexate) via OAT1/OAT3, organic cations (creatinine, metformin, cimetidine) via OCT2/MATE; ammoniagenesis from glutamine produces NH₄⁺ and new HCO₃⁻. The PCT is also the site of 1α-hydroxylase (calcitriol synthesis) and of renal gluconeogenesis.

Location: Renal cortex (convoluted part) and medullary rays/outer medulla (straight part).

Anatomy

Histology: Simple cuboidal epithelium with a tall brush border (microvilli), apical endocytic vesicles, abundant mitochondria in basolateral infoldings (intensely eosinophilic), indistinct lateral borders and a lumen often appearing occluded in sections.

Function

Reabsorb ≈65–67% of filtered Na⁺, Cl⁻, K⁺, Ca²⁺ and water (isosmotic)
Reabsorb ≈100% of glucose and amino acids, ≈80–90% of HCO₃⁻, ≈80% of phosphate, ≈50% of urea
Secrete organic anions and cations, including many drugs
Ammoniagenesis (acid excretion) and synthesis of calcitriol

Physiology: Glucose transport maximum (Tm) ≈375 mg/min; renal threshold ≈180–200 mg/dL (≈10–11 mmol/L) plasma glucose — glycosuria appears above it. Angiotensin II and sympathetic nerves stimulate NHE3; PTH and FGF23 inhibit NaPi-IIa; dopamine inhibits proximal Na⁺ reabsorption. Glomerulotubular balance keeps fractional reabsorption ≈constant when GFR changes.
Regulation: Angiotensin II (↑Na⁺/HCO₃⁻ reabsorption), PTH (↓phosphate reabsorption, ↑1α-hydroxylase), FGF23 (↓phosphate, ↓calcitriol), sympathetic nerves.

Clinical significance

Fanconi syndrome

Generalised PCT dysfunction (cystinosis, Wilson disease, multiple myeloma light chains, tenofovir, ifosfamide, outdated tetracyclines, lead) → glycosuria with normal blood glucose, aminoaciduria, phosphaturia (rickets/osteomalacia), uricosuria and proximal (type 2) RTA.

Drugs acting on the PCT

SGLT2 inhibitors (empagliflozin, dapagliflozin) cause glycosuria and natriuresis; acetazolamide inhibits carbonic anhydrase → HCO₃⁻ diuresis and hyperchloraemic acidosis (used for glaucoma, altitude sickness); mannitol acts osmotically in the PCT and descending limb. Probenecid blocks organic anion secretion (prolonging penicillin action).

Acute tubular necrosis

The straight S3 segment in the outer medulla is the most vulnerable to ischaemia; the PCT also concentrates nephrotoxins (aminoglycosides, cisplatin, contrast, myoglobin). Necrotic cells slough into the lumen as muddy-brown granular casts.

Test yourself

Which nephron segment reabsorbs the largest fraction of filtered sodium?

Thick ascending limb
Distal convoluted tubule
Proximal convoluted tubule
Cortical collecting duct

Answer: Proximal convoluted tubule

The PCT reabsorbs ≈65–67% of filtered Na⁺ and water isosmotically; the thick ascending limb ≈25%, the DCT ≈5–7% and the collecting duct ≈2–5%.

SGLT2 inhibitors such as empagliflozin act primarily on which part of the nephron?

Early proximal convoluted tubule (S1–S2)
Thick ascending limb
Distal convoluted tubule
Medullary collecting duct

Answer: Early proximal convoluted tubule (S1–S2)

SGLT2 (low-affinity, high-capacity) reabsorbs ≈90% of filtered glucose in the early PCT; SGLT1 in the S3 segment reabsorbs the remainder. Blocking SGLT2 causes glycosuria and mild natriuresis.