The Nephron: Structure & Function
The nephron is the fundamental structural and functional unit of the kidney, responsible for filtering the blood, regulating fluid and electrolyte balance, maintaining acid–base homeostasis, and eliminating metabolic waste. Each kidney contains approximately one million nephrons, and together they continuously process enormous volumes of plasma with remarkable precision. Although every nephron performs the same basic functions, its regional structure determines how efficiently it can concentrate urine, regulate solutes, and adapt to physiological stress. Understanding the detailed anatomy and segment-by-segment function of the nephron is essential for interpreting normal renal physiology and the mechanisms underlying kidney disease.
What You Need to Know
Each nephron is a highly specialised functional unit designed to filter plasma and precisely adjust its composition before it becomes urine. Every nephron consists of a renal corpuscle, which performs filtration, and a renal tubule, which modifies the filtrate through reabsorption and secretion. Although the structure of each nephron follows the same general plan, the organisation of its segments and blood supply allows different regions of the kidney to perform distinct physiological roles.
As filtrate flows through the nephron, each segment contributes in a specific way:
the glomerulus filters water and small solutes from the blood
the proximal convoluted tubule performs bulk reabsorption of water, electrolytes, and nutrients
the loop of Henle establishes the medullary osmotic gradient required for urine concentration
the distal convoluted tubule fine-tunes electrolyte and acid–base balance
the collecting ducts determine the final volume and concentration of urine under hormonal control
This regional specialisation allows the kidney to regulate fluid, electrolyte, and waste excretion with remarkable precision.
Nephrons are also divided into two functional types based on their location. Cortical nephrons are located mainly in the outer cortex and have short loops of Henle; they are responsible for most filtration and routine solute handling. Juxtamedullary nephrons originate near the corticomedullary junction and extend deep into the medulla, where their long loops of Henle and surrounding vasa recta generate and preserve the osmotic gradient that allows the kidneys to produce concentrated urine.
Beyond the Basics
The Renal Corpuscle: Filtration Interface
The renal corpuscle is designed to perform one task extremely efficiently: separate plasma into filtered fluid and retained blood. Blood enters the glomerulus through the afferent arteriole and exits via the efferent arteriole, which keeps pressure high within the capillary tuft. This elevated pressure drives filtration across the glomerular barrier.
The filtration barrier is formed by three integrated layers: the fenestrated endothelium, the glomerular basement membrane, and the podocytes of Bowman’s capsule. Together, they provide both size and charge selectivity, allowing water and small solutes to pass while excluding proteins and cells. The resulting ultrafiltrate contains the raw materials from which urine will be formed — water, electrolytes, glucose, amino acids, and metabolic waste — but none of the larger components needed to remain in the blood.
The Proximal Convoluted Tubule: Bulk Reabsorption
The proximal convoluted tubule is the nephron’s main recovery site. Because so much valuable material is filtered at the glomerulus, the PCT must rapidly reclaim it to prevent catastrophic losses. The dense brush border of microvilli increases membrane surface area, while abundant mitochondria supply the energy needed for active transport.
Sodium reabsorption drives most other solute and water movement in this segment. As sodium is transported back into the blood, glucose, amino acids, and bicarbonate are carried with it, and water follows osmotically. This allows the PCT to return large volumes of fluid to the circulation while keeping the filtrate close to plasma concentration. At the same time, the PCT actively secretes acids, drugs, and toxins, helping regulate pH and clear substances that should not remain in the body.
The Loop of Henle: Creating the Concentration Gradient
The loop of Henle does not directly concentrate urine, but it creates the medullary environment that makes concentration possible. Its descending limb allows water to leave but retains solutes, while its ascending limb removes solutes but retains water. This separation is the foundation of countercurrent multiplication.
As sodium and chloride are pumped into the medullary interstitium by the ascending limb, the medulla becomes progressively more hyperosmotic. When water later encounters this environment in the collecting ducts, it will be drawn out if ADH is present. Juxtamedullary nephrons, with their long loops extending deep into the medulla, are therefore essential for producing highly concentrated urine.
The Distal Convoluted Tubule: Precision Control
The distal convoluted tubule transitions the nephron from bulk processing to fine regulation. Here, sodium, potassium, hydrogen ions, and calcium are adjusted according to hormonal signals rather than fixed transport rules. This allows the kidney to respond to changes in blood pressure, electrolyte intake, and acid–base status.
Parathyroid hormone increases calcium reabsorption in the early DCT, linking kidney function to bone health. Aldosterone influences sodium and potassium handling in the later DCT, setting the stage for volume and potassium regulation in the collecting ducts.
The Collecting Duct System: Final Decision-Making
The collecting ducts act as the kidney’s final checkpoint. By the time filtrate reaches this segment, most processing is complete, but the most important decisions remain: how much water to conserve and how much acid or base to excrete.
ADH determines water permeability by controlling aquaporin insertion into the duct walls. When ADH is high, water leaves the tubule and concentrated urine is produced. When ADH is low, water remains in the tubule and dilute urine is excreted. Intercalated cells in this segment fine-tune acid–base balance by secreting hydrogen ions or bicarbonate depending on metabolic needs.
Cortical vs Juxtamedullary Nephrons
Cortical nephrons perform most filtration and routine solute handling, but juxtamedullary nephrons are responsible for the kidney’s concentrating ability. Their long loops and associated vasa recta generate and preserve the medullary gradient that allows water conservation. Without these specialised nephrons, humans would be unable to survive periods of dehydration.
Peritubular Capillaries & Vasa Recta
The blood vessels surrounding the tubules are as specialised as the tubules themselves. Peritubular capillaries have low pressure and high oncotic pull, making them ideal for reabsorbing fluid and solutes from cortical nephrons. The vasa recta, in contrast, function as countercurrent exchangers, allowing deep medullary tissue to be supplied with blood without washing away the osmotic gradient required for urine concentration.
Clinical Connections
Damage to specific nephron segments produces predictable patterns of renal dysfunction. Injury to the proximal tubule impairs reabsorption of glucose, bicarbonate, phosphate, and amino acids, leading to metabolic acidosis, electrolyte wasting, and nutritional depletion, as seen in Fanconi syndrome and toxic or ischaemic tubular injury.
The thick ascending limb of the loop of Henle is essential for sodium reabsorption and maintenance of the medullary gradient. Loop diuretics act here to block sodium transport, producing powerful diuresis and natriuresis. This makes them highly effective for treating pulmonary oedema and heart failure, but also explains why they commonly cause dehydration, hypokalaemia, and metabolic alkalosis.
The distal convoluted tubule fine-tunes sodium, potassium, and calcium handling. Thiazide diuretics act in this segment, leading to:
reduced sodium reabsorption
increased calcium retention
This is why they lower blood pressure and reduce kidney stone risk but may cause hyponatraemia and hypokalaemia.
Dysfunction of the collecting ducts disrupts the body’s ability to regulate water and acid–base balance, producing conditions such as diabetes insipidus and renal tubular acidosis. Because this segment makes the final decisions about urine composition, damage here often results in:
large-volume dilute urine or severe dehydration
metabolic acidosis or alkalosis
Understanding which nephron segment is affected allows clinicians to predict laboratory abnormalities, identify the underlying mechanism, and choose targeted therapy.
Concept Check
Why does the proximal convoluted tubule reabsorb such a large proportion of filtered solutes?
How does the loop of Henle generate the medullary osmotic gradient?
Why are juxtamedullary nephrons essential for urine concentration?
How does ADH alter water handling in the collecting ducts?
Why does injury to different nephron segments produce different clinical effects?