Table of Contents
Overview: From Blood Plasma to Final Urine
In the nephron, urine is formed in three main steps:
- Glomerular filtration – bulk filtration of blood plasma into the nephron
- Tubular reabsorption – taking useful substances back into the blood
- Tubular secretion – adding more unwanted substances from blood into the tubule
By the time the fluid leaves the collecting duct, it has been transformed from glomerular filtrate (very similar to blood plasma without proteins) into final urine (concentrated waste with carefully adjusted water and salt content).
Each segment of the nephron has a characteristic role in this transformation.
Step 1: Glomerular Filtration in the Renal Corpuscle
Filtration occurs in the renal corpuscle, made of:
- Glomerulus – a tuft of capillaries fed by the afferent arteriole and drained by the efferent arteriole
- Bowman’s capsule – a surrounding cup that collects the filtrate
The Filtration Barrier
Blood is filtered through a multi-layer barrier:
- Fenestrated capillary endothelium – capillary wall with many pores; blocks cells but allows plasma through.
- Basement membrane – negatively charged mesh; repels large proteins.
- Podocytes – specialized cells of Bowman’s capsule with interdigitating “foot processes” and filtration slits.
Together they:
- Allow: water, ions (Na⁺, K⁺, Cl⁻), small molecules (glucose, amino acids, urea, small hormones)
- Block: blood cells, platelets, most plasma proteins, protein-bound molecules
The resulting fluid in Bowman’s space is the glomerular filtrate.
Driving Forces: Filtration Pressure
Filtration is driven by blood pressure. The net filtration pressure is determined by:
- Hydrostatic pressure in glomerular capillaries (pushes fluid out)
- Hydrostatic pressure in Bowman’s capsule (pushes fluid back in)
- Colloid osmotic (oncotic) pressure of plasma proteins (draws water back into capillaries)
Filtration occurs as long as:
$$
P_{\text{glomerular}} - P_{\text{Bowman}} - \pi_{\text{plasma}} > 0
$$
The glomerular filtration rate (GFR) is the volume filtered per unit time, usually kept nearly constant by kidney autoregulation (covered elsewhere).
Step 2: Tubular Reabsorption
Most of the filtered water and solutes are reclaimed along the tubule and returned to the blood in the peritubular capillaries and vasa recta. This is highly selective and region-specific.
Proximal Convoluted Tubule (PCT): Bulk Reabsorption
The PCT returns the largest fraction of filtrate to the bloodstream.
- Water
- Reabsorbed in large amounts by osmosis; the PCT is highly water-permeable.
- Na⁺ (sodium)
- Actively transported out of tubular cells into interstitial fluid by the Na⁺/K⁺-ATPase in the basolateral membrane.
- This creates a low Na⁺ concentration inside the cell, driving Na⁺ entry from the lumen via:
- Symporters (cotransporters) – Na⁺ plus glucose, amino acids, phosphate, etc.
- Antiporters (exchangers) – Na⁺ in, H⁺ out.
- Glucose and amino acids
- Almost completely reabsorbed via Na⁺-dependent cotransport on the apical side, and then facilitated diffusion on the basolateral side into the interstitium.
- If blood glucose is very high (e.g., in untreated diabetes), transporters saturate → glucose remains in tubule → appears in urine (glucosuria).
- Bicarbonate (HCO₃⁻)
- Not directly transported; instead, filtered HCO₃⁻ reacts with H⁺ secreted into the lumen to form CO₂ and H₂O, which diffuse back into the cell.
- Inside the cell, carbonic anhydrase converts CO₂ and H₂O back into H⁺ and HCO₃⁻; HCO₃⁻ is transported into the blood.
- This mechanism plays a major role in acid–base balance.
- Other ions
- Cl⁻, K⁺, Ca²⁺, Mg²⁺ are partly reabsorbed via paracellular (between cells) and transcellular routes.
- Small proteins and peptides
- Taken up by endocytosis, then degraded into amino acids.
By the end of the PCT:
- Around 65–70% of filtered water and Na⁺ is reabsorbed.
- Almost all glucose and amino acids have been recovered.
- Filtrate volume is drastically reduced, but its osmolarity remains similar to plasma (isotonic) because water follows solute.
Loop of Henle: Creating the Medullary Gradient
The loop of Henle consists of:
- Descending thin limb
- Ascending thin limb (in some nephrons)
- Ascending thick limb
Together, they establish a concentration gradient in the kidney medulla (cortex: less salty; inner medulla: very salty). This gradient is essential for concentrating urine.
Descending Limb
- Highly permeable to water via aquaporins
- Low permeability to Na⁺ and other solutes
As the filtrate descends into the increasingly salty medulla:
- Water leaves the tubule by osmosis into the hyperosmotic interstitium.
- Filtrate becomes more concentrated (osmolarity rises).
Ascending Limb
- Impermeable to water
- Actively and passively transports NaCl out of the tubule:
- Thick ascending limb: uses the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC) to move these ions from lumen into cells; then they pass to interstitium.
- This dilutes the tubular fluid while increasing medullary interstitial osmolarity.
Because the descending limb loses water and the ascending limb pumps out salt but not water, a countercurrent multiplier system arises, leading to a steep osmotic gradient from cortex to medulla.
Distal Convoluted Tubule (DCT) and Collecting Duct: Fine-Tuning
In these segments, the kidney performs hormone-controlled regulation of salts, water, and pH.
Distal Convoluted Tubule (Early Portion)
- Further NaCl reabsorption via a Na⁺-Cl⁻ cotransporter.
- Still relatively impermeable to water in the absence of antidiuretic hormone (ADH).
- Filtrate here is often hypotonic (less concentrated than plasma).
Late Distal Tubule and Collecting Duct
Key cell types:
- Principal cells – regulate Na⁺, K⁺, and water.
- Intercalated cells – regulate acid–base balance (H⁺ and HCO₃⁻ handling).
Main processes:
- Na⁺ reabsorption and K⁺ secretion
- Controlled largely by the hormone aldosterone, which:
- Increases the number and activity of Na⁺ channels (on the lumen side) and Na⁺/K⁺-ATPase (on the basolateral side).
- Causes more Na⁺ reabsorption and more K⁺ secretion into the tubular fluid.
- Water reabsorption
- Controlled mainly by antidiuretic hormone (ADH, vasopressin).
- In the presence of ADH:
- More aquaporin water channels are inserted into principal cells’ luminal membranes.
- The collecting duct becomes highly permeable to water.
- Water moves out of the tubule into the salty medullary interstitium → urine becomes concentrated.
- Without ADH:
- Collecting duct is relatively water-impermeable.
- Large volume of dilute urine is produced.
- Urea handling
- In the inner medullary collecting duct, urea transporters can reabsorb urea into the medulla.
- Urea contributes to the medullary osmotic gradient, helping further water reabsorption.
- Acid–base regulation
- Intercalated cells secrete H⁺ (via H⁺-ATPases) and reabsorb or secrete HCO₃⁻ depending on the body’s pH status.
- This adjusts urine pH and contributes to blood pH stabilization.
By modulating transport in these segments, the kidney fine-tunes:
- Final urine volume
- Final urine osmolarity
- Excretion/retention of Na⁺, K⁺, H⁺, HCO₃⁻, and other ions
Step 3: Tubular Secretion
Secretion adds substances from peritubular capillary blood or tubular cells into the tubular fluid. It occurs mainly in the PCT and DCT/collecting duct.
Important secreted substances:
- H⁺ (protons) – for acid–base regulation (especially in PCT and intercalated cells).
- K⁺ (potassium) – primarily in late DCT and collecting duct under aldosterone control.
- Organic anions and cations – including many drugs (e.g., some antibiotics, diuretics), metabolic by-products, and toxins.
- Ammonium ions (NH₄⁺) – formed from glutamine; secretion helps excrete acid and conserve bicarbonate.
Secretion allows the kidney to eliminate compounds that:
- Are not freely filtered, or
- Need to be excreted in amounts greater than filtered load.
From Collecting Duct to Final Urine
After passing through the collecting ducts, the fluid is now urine:
- Containing nitrogenous wastes (mainly urea, plus uric acid, creatinine)
- With exactly adjusted water and salt content for the organism’s needs at that moment
- With a composition that reflects acid–base regulation (variable H⁺ and HCO₃⁻ content)
Path to excretion:
- Collecting ducts → join into larger ducts in the renal papillae
- Urine drains into minor and major calyces
- Then into the renal pelvis
- Down the ureter to the bladder
- Finally excreted via the urethra
Summary of Segment Functions in Urine Formation
- Glomerulus/Bowman’s capsule – filters plasma → primary filtrate (proteins, cells retained).
- PCT – bulk reabsorption (most water, Na⁺, all glucose and amino acids; major bicarbonate reclamation).
- Loop of Henle – creates medullary osmotic gradient; descending limb: water out; ascending limb: salts out, no water.
- DCT (early) – further NaCl reabsorption; fluid becomes more dilute.
- Late DCT and collecting duct – hormone-regulated fine-tuning of Na⁺, K⁺, water, and pH; determines final urine concentration and volume.
Through these coordinated processes, the nephron converts a large, relatively unselective filtrate into a small volume of precisely composed urine, helping maintain homeostasis of body fluids.