Difficulty: Intermediate to Advanced | Prerequisites: Part 1 of these notes (kidney anatomy and nephron structure), membrane transport mechanisms (active transport, osmosis, symport, facilitated diffusion).
Now that you know the anatomy, this section explains what the nephron actually does with blood. Urine formation is a three-step process: filtration pushes fluid out of the blood, reabsorption pulls the useful stuff back in, and secretion adds a few extras that need to be eliminated. The proximal convoluted tubule does the heavy lifting for reabsorption, the loop of Henle builds the concentration gradient that lets you concentrate urine, and the distal tubule and collecting duct fine-tune the final product under hormonal control. If you skipped Part 1, go back: you need to know the nephron segments and their histology before this will make sense.
The kidneys filter about 180 litres of fluid per day, but only 1 to 2 litres become urine because 99% of the filtrate is reabsorbed. Filtration is a passive, pressure-driven process at the glomerulus. Tubular reabsorption (mostly in the PCT) reclaims water, glucose, amino acids, and ions. Tubular secretion adds waste products and drugs to the filtrate for elimination.
Filtrate
The fluid that passes from blood in the glomerular capillaries across the filtration membrane into the Bowman capsule. It contains water, small molecules, and ions, but normally no blood cells or large proteins. Think of it as "pre-urine" that still contains almost everything useful.
Renal fraction
The percentage of total cardiac output that flows through the kidneys. It ranges from 12% to 30% and averages about 21%.
Renal blood flow rate
The rate of whole blood flow through the kidneys, calculated as cardiac output multiplied by the renal fraction. The average value is approximately 1176 mL/min.
Renal plasma flow rate
The rate at which plasma (not whole blood) flows through the kidneys. Calculated as renal blood flow rate multiplied by the fraction of blood that is plasma. Average is about 650 mL/min.
Glomerular filtration rate (GFR)
The volume of filtrate produced per unit time. The kidneys produce about 180 L/day. GFR equals the renal plasma flow rate multiplied by the filtration fraction.
Filtration fraction
The proportion of plasma entering the kidney that is actually filtered into the glomerular capsule. Averages about 19%.
Filtration pressure
The net pressure gradient that drives fluid from the glomerular capillaries across the filtration membrane into the Bowman capsule. It is the result of three opposing pressures.
Glomerular capillary pressure (GCP)
Blood pressure inside the glomerular capillary, which promotes filtration by pushing fluid out. Approximately 50 mm Hg.
Capsule hydrostatic pressure (CHP)
The pressure exerted by filtrate already sitting in the Bowman capsule, which opposes filtration. Approximately 10 mm Hg.
Blood colloid osmotic pressure (BCOP)
Osmotic pressure created by proteins remaining in the blood, which draws water back into the capillary and opposes filtration. Approximately 30 mm Hg. BCOP increases along the length of the glomerular capillary as fluid leaves and protein concentration rises.
Tubular reabsorption
The process by which water and useful solutes are transported from the filtrate in the tubule lumen back into the blood via the peritubular capillaries. About 99% of the filtrate is reabsorbed.
Tubular secretion
The transfer of substances from the blood (via peritubular capillaries) into the tubular filtrate. This handles metabolic by-products, drugs, and ions (especially H+ and K+) that may not have been filtered or need additional removal.
Apical membrane
The surface of a tubule cell that faces the lumen (the filtrate side). In the PCT, this surface is covered in microvilli.
Basal membrane
The surface of a tubule cell that faces the interstitial fluid and peritubular capillaries.
Symport (cotransport)
A type of secondary active transport in which two substances cross a membrane in the same direction on the same carrier protein. In the PCT, Na+ is symported with glucose, amino acids, and other solutes across the apical membrane.
Transport maximum (Tm)
The maximum rate at which a substance can be reabsorbed by the tubule cells. It is limited by the number of available carrier proteins. When plasma concentration of a substance exceeds the Tm, the excess appears in the urine.
Renal threshold
The plasma concentration of a substance at which it begins to appear in the urine because the transport maximum has been exceeded.
Glucosuria
The presence of glucose in the urine, occurring when blood glucose exceeds the renal threshold (as in uncontrolled diabetes mellitus).
Plasma clearance
The volume of plasma completely cleared of a particular substance per minute. Used clinically to estimate GFR (using creatinine) or renal plasma flow (using para-aminohippuric acid, PAH).
Creatinine
A waste product of muscle metabolism that is freely filtered, not reabsorbed, and not significantly secreted. Its clearance is used to estimate GFR.
Para-aminohippuric acid (PAH)
A substance that is both filtered and actively secreted into the tubule, meaning almost all of it is removed from the blood in a single pass. Its clearance is used to estimate renal plasma flow.
Filtration is nonselective. Blood pressure in the glomerular capillaries forces water and small solutes (ions, glucose, amino acids, urea) across the filtration membrane into the Bowman capsule. Large proteins and blood cells cannot pass. The result is called filtrate.
Filtration pressure is the net force driving filtration, calculated as:
Filtration pressure = GCP - CHP - BCOP
Using typical values: 50 - 10 - 30 = 10 mm Hg net filtration pressure.
Three features maintain the high GCP that makes filtration efficient:
Low resistance in the afferent arterioles (blood flows in easily).
Low resistance in the glomerular capillaries themselves.
High resistance in the efferent arterioles (the narrow exit keeps pressure high inside the glomerulus).
Key numbers:
Renal fraction: ~21% of cardiac output
Renal blood flow rate: ~1176 mL/min
Renal plasma flow rate: ~650 mL/min
GFR: ~180 L/day
Filtration fraction: ~19%
Average urine output: 1 to 2 L/day (meaning 99%+ of filtrate is reabsorbed)
Filtration membrane components (three layers, from blood side to capsule side):
Fenestrated glomerular capillary endothelium
Basement membrane
Podocytes of the visceral layer
Some small proteins (albumin, small protein hormones) do enter the filtrate, but they are reabsorbed and metabolised by PCT cells. Under normal conditions, very little protein appears in urine.
Clinical note: in glomerular nephritis, the filtration membrane becomes damaged and more permeable. Proteins leak into the filtrate, raising the osmotic pressure of the filtrate itself, which draws more water out of the blood and increases urine volume.
Hypertension can damage glomerular capillaries over time, which is one reason chronic high blood pressure leads to kidney disease.
Reabsorption is the process of reclaiming water and useful solutes from the filtrate. It occurs along the entire length of the tubule but is most extensive in the PCT.
Substances reabsorbed include sodium, potassium, calcium, bicarbonate, chloride, glucose, amino acids, and water. Overall, about 99% of filtrate volume is returned to the blood. What remains (urea, uric acid, creatinine, excess potassium, and other waste) becomes urine.
The PCT is the workhorse of reabsorption. By the time filtrate leaves the PCT, its volume has been reduced by roughly 65%.
The driving force behind most PCT reabsorption is the Na+-K+ ATPase pump on the basal membrane. This pump actively transports Na+ out of the tubule cell into the interstitial fluid, keeping intracellular Na+ concentration low. That concentration gradient then pulls Na+ from the filtrate into the cell across the apical membrane.
Na+ entry across the apical membrane is coupled via symport carriers with glucose, amino acids, and other solutes. The Na+ gradient provides the energy (secondary active transport).
Each carrier protein binds specifically to one solute plus Na+.
Once inside the cell, the symported molecules cross the basal membrane by facilitated diffusion or symport into the interstitial fluid.
The number of carrier proteins is finite. This sets the transport maximum. In diabetes mellitus, blood glucose is so high that the filtrate glucose concentration exceeds the Tm, and glucose spills into the urine (glucosuria).
Paracellular transport: some solutes (K+, Ca2+, Mg2+) also diffuse between tubule cells through lateral surfaces into the interstitial fluid, driven by concentration gradients that build as water is reabsorbed.
Water reabsorption in the PCT follows solute reabsorption by osmosis. As solutes leave the filtrate, the remaining fluid becomes slightly more concentrated, drawing water out through the tubule wall. This process is obligatory and constant (not hormonally regulated).
The nephron loop has segments with very different permeability properties:
Descending thin segment: highly permeable to water, moderately permeable to solutes (urea, Na+, other ions). As the loop dips into the increasingly concentrated medullary interstitial fluid, water leaves by osmosis and some solutes diffuse in. By the bottom of the loop, filtrate volume is reduced by another 15% and its concentration has risen to about 1200 mOsm/kg.
Ascending thin segment: impermeable to water but permeable to solutes. Solutes diffuse out of the tubule into the (relatively more dilute) interstitial fluid as the limb climbs toward the cortex.
Ascending thick segment: impermeable to both water and solutes by passive means. Instead, the cells use ATP-powered pumps and symporters to actively transport Na+, K+, and Cl- from the filtrate into the interstitial fluid. This active transport is what builds and maintains the high medullary concentration gradient.
By the end of the nephron loop, the filtrate inside the tubule is very dilute, about 100 mOsm/kg, while the surrounding interstitial fluid in the cortex is about 300 mOsm/kg. The filtrate entering the DCT is therefore hypotonic relative to the interstitial fluid.
Water reabsorption here is variable and controlled by antidiuretic hormone (ADH).
The permeability of the DCT and collecting duct walls to water depends on whether ADH is present.
K+ and H+ absorption or secretion occurs here under hormonal control (primarily aldosterone), depending on body conditions.
Urine concentration can range from very dilute (high volume, low concentration) to very concentrated (low volume, high concentration) depending on hormonal signals.
Tubular secretion moves substances from the blood into the filtrate, typically in the PCT and DCT. It handles materials that may not have been filtered at the glomerulus, or that need to be removed in greater quantities.
Ammonia: produced by deamination of amino acids within tubule epithelial cells; diffuses passively into the lumen.
H+, K+, penicillin, PAH: actively secreted into the nephron.
H+ secretion in the proximal tubule occurs by countertransport with Na+. H+ may come from the peritubular capillaries or from the reaction of CO2 and water within tubule cells. Na+ and HCO3- are cotransported across the basal membrane into the interstitial fluid.
H+ and K+ secretion in the distal tubule also occurs by countertransport. Na+ and K+ are cotransported across the basal membrane into the interstitial fluid.
Urea enters the filtrate at the glomerulus. As water is reabsorbed, urea concentration in the filtrate rises. The nephron walls are only moderately permeable to urea, so only 40% to 60% is passively reabsorbed. The remainder is excreted.
Urate ions, creatinine, sulfates, phosphates, and nitrates are partially reabsorbed, leaving a high concentration in the final urine.
Toxic substances are also eliminated via this route.
Plasma clearance is the clinical measure of how efficiently the kidneys remove a substance from the blood.
Creatinine clearance is used to estimate GFR because creatinine is freely filtered, not reabsorbed, not secreted, and not metabolised by the kidneys.
PAH clearance is used to estimate renal plasma flow because PAH is both filtered and almost completely secreted, so nearly all of it is removed in one pass.
Filtration pressure:
Filtration pressure = GCP - CHP - BCOP
Example: 50 mm Hg - 10 mm Hg - 30 mm Hg = 10 mm Hg
GFR:
GFR = Renal plasma flow rate x Filtration fraction
Renal blood flow rate:
Renal blood flow rate = Cardiac output x Renal fraction
Renal plasma flow rate:
Renal plasma flow rate = Renal blood flow rate x Fraction of blood that is plasma
Plasma clearance measurements are part of routine clinical practice. When a patient's estimated GFR (based on creatinine clearance) drops below normal, it signals declining kidney function, one of the earliest indicators of chronic kidney disease. The concept of transport maximum is why patients with uncontrolled diabetes produce large volumes of glucose-containing urine: their blood sugar overwhelms the PCT's ability to reabsorb glucose, and the unreabsorbed glucose holds water in the tubule by osmosis, increasing urine output.
Students often think filtration is selective. It is not. Filtration at the glomerulus is a passive, pressure-driven process that separates substances based on size and charge only. The selectivity comes later, during reabsorption and secretion.
Students frequently assume that all reabsorption is active. Much of the water reabsorption in the PCT and descending limb is passive (by osmosis), following the active transport of solutes.
The ascending limb of the loop of Henle is sometimes thought to reabsorb water. It does not; it is impermeable to water. This impermeability is precisely what allows the filtrate to become dilute by the time it reaches the DCT.
Glucose in the urine is sometimes assumed to mean the kidneys are broken. In diabetes mellitus, the kidneys are working normally; it is the blood glucose that is too high, exceeding the transport maximum.
Be able to calculate filtration pressure from GCP, CHP, and BCOP values.
Know which substances are reabsorbed where (PCT does the bulk; loop of Henle handles water and ions; DCT and collecting duct are hormonally regulated).
Understand the role of the Na+-K+ pump in driving secondary active transport in the PCT.
Know the permeability differences between the descending limb (water-permeable), thin ascending limb (solute-permeable, water-impermeable), and thick ascending limb (actively transports ions, impermeable to both).
Be able to explain why filtrate is dilute (100 mOsm/kg) when it reaches the DCT.
Understand transport maximum and its connection to glucosuria in diabetes.
Know what plasma clearance measures and which substances are used to estimate GFR vs. renal plasma flow.
1. True or false: Filtration at the glomerulus is a selective process. A: False. Filtration is nonselective, based on size and charge.
2. Fill in the blank: The net filtration pressure using standard values (GCP 50, CHP 10, BCOP 30) is ______ mm Hg. A: 10 mm Hg.
3. True or false: The ascending limb of the loop of Henle is permeable to water. A: False. It is impermeable to water.
4. Fill in the blank: By the end of the PCT, filtrate volume has been reduced by approximately ______%. A: 65%.
5. True or false: Creatinine clearance is used to estimate renal plasma flow. A: False. Creatinine clearance estimates GFR. PAH clearance estimates renal plasma flow.
Q: What are the three pressures that determine filtration pressure, and which promotes versus opposes filtration?
A: Glomerular capillary pressure (GCP) promotes filtration. Capsule hydrostatic pressure (CHP) and blood colloid osmotic pressure (BCOP) both oppose filtration. Filtration pressure = GCP - CHP - BCOP.
Q: Why does the concentration of filtrate at the bottom of the loop of Henle reach approximately 1200 mOsm/kg?
A: The descending limb is highly permeable to water and moderately permeable to solutes. As it descends into the medulla, where interstitial fluid is progressively more concentrated, water leaves by osmosis and some solutes enter by diffusion, concentrating the filtrate to about 1200 mOsm/kg.
Q: Explain how diabetes mellitus leads to glucosuria and increased urine volume.
A: In diabetes mellitus, high blood glucose means the filtrate contains more glucose than the transport maximum of the PCT carrier proteins can handle. The excess glucose remains in the filtrate. Because glucose is an osmotically active solute, it holds water in the tubule, reducing reabsorption and increasing urine volume.
Q: Describe the role of the Na+-K+ ATPase in proximal tubule reabsorption.
A: The Na+-K+ ATPase on the basal membrane actively pumps Na+ out of the tubule cell, keeping intracellular Na+ low. This creates a steep concentration gradient that drives Na+ into the cell from the filtrate across the apical membrane via symport carriers, bringing glucose, amino acids, and other solutes along with it (secondary active transport).
Q: What is the functional significance of the thick ascending limb being impermeable to water?
A: Because ions are actively transported out of the thick ascending limb but water cannot follow, the filtrate becomes progressively more dilute while the medullary interstitial fluid becomes more concentrated. This separation of water and solute is essential for establishing the medullary concentration gradient and for the kidney's ability to produce concentrated urine.
The transport mechanisms here (active transport, symport, osmosis, facilitated diffusion) draw directly on the membrane physiology covered in earlier chapters. The role of Na+ as the primary driver of reabsorption connects to the broader importance of sodium in fluid balance and blood pressure regulation (Chapter 27). The clinical relevance of GFR and creatinine clearance ties into pathophysiology and pharmacology, since many drugs are dosed based on kidney function.
urine formation, glomerular filtration, filtration pressure, GFR, glomerular filtration rate, filtrate, renal fraction, renal blood flow rate, renal plasma flow rate, filtration fraction, tubular reabsorption, tubular secretion, proximal convoluted tubule, PCT reabsorption, Na-K ATPase, sodium potassium pump, symport, secondary active transport, transport maximum, renal threshold, glucosuria, loop of Henle reabsorption, descending limb, ascending limb, thick segment, thin segment, distal convoluted tubule, collecting duct, plasma clearance, creatinine clearance, PAH, para-aminohippuric acid, urea, filtration membrane, BCOP, GCP, CHP, anatomy and physiology chapter 26