Q2 LONG ANSWER 10M ★ High-yield

Describe tubular reabsorption in the different parts of the nephron. Explain glucose reabsorption with transport maximum and renal threshold.

Physiology · 1st Professional — Pre-Clinical

Introduction

Tubular reabsorption = movement of substances from the tubular lumen back into the peritubular capillary blood.

Of 180 L filtered per day, about 178.5 L is reabsorbed
Mechanisms — active (against gradient, needs ATP) and passive (diffusion, osmosis, solvent drag)

Proximal Convoluted Tubule — the Workhorse

Substance	Amount reabsorbed in PCT	Mechanism
Glucose	100%	Secondary active — SGLT-2 (90%) and SGLT-1
Amino acids	100%	Secondary active, Na+-linked
Na+	65–70%	Active (Na+–K+ pump basolaterally)
HCO3−	85–90%	Via H+ secretion + carbonic anhydrase
Water	65%	Passive, obligatory (osmosis)
K+	65%	Passive and active
Urea	50%	Passive diffusion

PCT reabsorption is iso-osmotic — solute and water are reabsorbed in equal proportion, so tubular fluid leaves the PCT at 300 mOsm/kg
PCT cells have a brush border and abundant mitochondria — adapted for bulk active transport

Glucose Reabsorption and Transport Maximum

Transport maximum (Tm) = the maximum rate at which a substance can be reabsorbed, when all carriers are saturated.Tm for glucose = 375 mg/min (male), 300 mg/min (female)

Glucose in lumen → SGLT on apical membrane (Na+ co-transport) → Into the cell against its gradient → GLUT-2 on basolateral membrane → Into blood by facilitated diffusion

Term	Definition	Value
Renal threshold	Plasma level at which the substance first appears in urine	180 mg/dL
Tm	Maximum reabsorptive capacity	375 mg/min
Splay	The rounding of the curve between threshold and Tm, because not all nephrons have identical Tm	—

Loop of Henle

Segment	Permeable to	Impermeable to	Effect
Descending limb	Water (aquaporin-1)	Solutes	Fluid becomes hypertonic (1200 mOsm at the tip)
Thin ascending limb	NaCl (passive)	Water	Dilution begins
Thick ascending limb	NKCC2 co-transporter — active NaCl reabsorption	Water	Fluid becomes hypotonic (100 mOsm)

The thick ascending limb is therefore called the diluting segment
It reabsorbs 25% of filtered Na+
Furosemide blocks NKCC2 → the most powerful class of diuretic

Distal Tubule and Collecting Duct

Segment	Transport	Regulated by
Early DCT	Na+–Cl− co-transporter (NCC); Ca2+ reabsorption	Thiazides block NCC; PTH ↑ Ca2+
Late DCT / collecting duct — principal cells	Na+ reabsorption via ENaC; K+ secretion	Aldosterone; blocked by spironolactone and amiloride
Intercalated cells	H+ secretion, HCO3− handling	Acid–base status
Collecting duct — water	Facultative water reabsorption via aquaporin-2	ADH

Glomerulotubular Balance

Glomerulotubular balance = the intrinsic ability of the tubule to reabsorb a constant fraction (about 65%) of the filtered load, whatever the GFR.

Prevents large swings in urine output when GFR changes
Mechanism — ↑ GFR raises the filtration fraction → ↑ peritubular capillary oncotic pressure → ↑ reabsorption
Works together with tubuloglomerular feedback as a second line of defence

Summary of Segmental Handling

Segment	Na+ reabsorbed	Water	Tubular fluid osmolality
PCT	65–70%	Obligatory, 65%	300 (iso-osmotic)
Loop of Henle	25%	15%	100 (hypo-osmotic)
DCT	5%	Little	100
Collecting duct	3%	Facultative (ADH)	50–1200

Tubular Secretion

Substances secreted — H+, K+, NH3, creatinine, PAH, penicillin, salicylates, diuretics
PAH is both filtered and secreted → almost completely cleared in one pass → used to measure renal plasma flow

Applied Aspects

Glycosuria — appears when blood glucose exceeds the renal threshold of 180 mg/dL. In renal glycosuria the threshold is lowered although blood glucose is normal
Pregnancy → ↑ GFR lowers the threshold → benign glycosuria
SGLT-2 inhibitors (dapagliflozin) deliberately block glucose reabsorption → glycosuria → used to treat type 2 diabetes
Fanconi syndrome — generalised PCT defect → glycosuria, aminoaciduria, phosphaturia, bicarbonate loss

All questions in Renal System

Every Physiology chapter →