Nephron Structure and the Stages of Urine Formation

The nephron is the functional unit of the kidney, and it forms urine in three stages: ultrafiltration of blood in the glomerulus, selective reabsorption of useful substances along the tubule and secretion and concentration of the remaining fluid as urine. In brief: each kidney contains about one million nephrons. Blood pressure forces water, glucose, urea and salts out of the glomerulus into the capsule, but not blood cells and large proteins. Almost all the glucose and most of the water are then reabsorbed. What remains is urine, which contains water, urea and excess salts.

The kidneys filter the whole blood volume about 60 times per day. This guide describes the structure of the kidney and nephron, explains each stage of urine formation, compares the composition of blood, filtrate and urine, works through a filtration calculation and corrects common mistakes.

What is the structure of the kidney?

The kidney has three main regions that can be seen in a section: the outer cortex, the inner medulla with cone-shaped pyramids and the renal pelvis, a funnel-shaped space that collects urine and leads to the ureter. Blood arrives through the renal artery, which branches into smaller arterioles, and leaves through the renal vein. Each kidney contains about one million nephrons and many collecting ducts.

What is the structure of a nephron?

A nephron is a microscopic tube, about 3 centimeters long when stretched out, that is closed at one end. It has the following parts, in order.

1. Bowman’s capsule: a cup-shaped structure in the cortex that surrounds the glomerulus.
2. Glomerulus: a knot of capillaries inside the capsule. Blood enters through a wide afferent arteriole and leaves by a narrower efferent arteriole, which keeps the pressure in the glomerulus high.
3. Proximal convoluted tubule: a coiled tube in the cortex. Its cells have microvilli and many mitochondria, for reabsorption.
4. Loop of Henle: a hairpin-shaped tube that dips into the medulla (descending limb) and returns to the cortex (ascending limb). It creates a salt gradient in the medulla.
5. Distal convoluted tubule: a second coiled tube in the cortex, for fine adjustment of salts and pH.
6. Collecting duct: receives fluid from many nephrons, passes through the medulla and carries urine to the renal pelvis. It is the site where water reabsorption is controlled by the hormone ADH.

How does ultrafiltration work?

Ultrafiltration takes place in the glomerulus and Bowman’s capsule. The blood pressure in the glomerulus is high, about 7 to 8 kPa (compared with around 1 to 2 kPa in other capillaries), because the efferent arteriole is narrower than the afferent. This pressure forces fluid out of the capillaries through three layers: the capillary wall (with pores), the basement membrane (a gel-like layer which acts as a filter) and the cells of the capsule (podocytes, with slits between them).

Small molecules pass through: water, glucose, amino acids, urea, salts and vitamins. Large molecules, such as plasma proteins, and blood cells are too large and stay in the blood. The fluid in the capsule is called the glomerular filtrate. About 20 percent of the plasma that passes through the glomerulus is filtered. The total filtration rate in an adult (glomerular filtration rate, GFR) is about 125 mL per minute for both kidneys, or 180 liters per day. Protein or blood in urine is a sign of damage to the filter.

What is selective reabsorption?

About 99 percent of the filtrate is reabsorbed, and the body would lose all its water in minutes otherwise. The main steps are:

• Proximal tubule: all of the glucose and amino acids, most of the salts (about two thirds of sodium) and about two thirds of the water are reabsorbed. Glucose and amino acids move back by active transport and facilitated diffusion. Water follows by osmosis. This region is adapted with a brush border of microvilli and many mitochondria for active transport. If the blood glucose concentration is very high, as in untreated diabetes, the carriers become saturated, and glucose appears in the urine.
• Loop of Henle: builds up a high concentration of salt in the medulla (the countercurrent multiplier). Water leaves the descending limb by osmosis, and salt is pumped out of the ascending limb.
• Distal tubule and collecting duct: adjust sodium, potassium and acidity, and water reabsorption is controlled by the hormone ADH.

The details of water control are covered in the next article.

How is urine formed and concentrated?

After reabsorption, the remaining fluid flows through the collecting duct, where the surrounding medulla has a high salt concentration. If the body needs to conserve water, more water leaves the collecting duct by osmosis, and the urine becomes concentrated. Urine is normally pale yellow, from the pigment urochrome, and is about 95 percent water, with urea (about 2 percent), salts and other wastes. The kidney can produce urine that is up to about four times more concentrated than blood in humans. Urine from a healthy person contains no glucose, protein or blood cells.

Some substances are added to the filtrate by tubular secretion, in which cells transfer substances from the blood into the tubule. Examples are hydrogen ions, potassium ions and some drugs such as penicillin.

Blood, filtrate and urine compared

Compare the columns to understand the processes. The absence of protein from the filtrate shows ultrafiltration. The presence of glucose in the filtrate, but not in the urine, shows selective reabsorption. The much higher urea concentration in urine (about 60 times the plasma concentration) shows the removal of water. The values are typical and vary with diet and hydration.

Worked example: filtration and reabsorption volumes

Assume a GFR of 125 mL/min, urine production of 1 mL/min, and a plasma glucose concentration of 5 mmol/L.

1. Filtrate per day: 125 mL/min × 60 × 24 = 180 000 mL = 180 liters.
2. Urine per day: 1 mL/min × 1 440 min = 1 440 mL ≈ 1.4 liters.
3. Water reabsorbed: 180 − 1.44 ≈ 178.6 liters. As a percentage: 178.6 ÷ 180 = 99.2 percent.
4. Glucose filtered per minute: 125 mL = 0.125 L; 0.125 × 5 mmol/L = 0.625 mmol/min. In urine of a healthy person, the amount is practically zero, so all was reabsorbed.
5. Concentration factor for urea: urine contains 2 g/100 mL of urea and the filtrate 0.03 g/100 mL, so urea is 2 ÷ 0.03 ≈ 67 times more concentrated in urine.

Now compare this with water. The volume of filtrate is 180 ÷ 1.44 ≈ 125 times the volume of urine. If none of the urea were reabsorbed, its concentration would rise 125-fold. The measured increase of about 67-fold means that about 67 ÷ 125 ≈ 54 percent of the filtered urea is excreted, and the remaining 46 percent is reabsorbed passively. The numbers are approximate.

How was kidney function discovered?

Marcello Malpighi described the glomerulus in the 1660s. William Bowman described the capsule in 1842. Carl Ludwig proposed in 1844 that urine is formed by filtration under pressure, and Rudolf Heidenhain suggested secretion. Arthur Cushny’s work in 1917 supported the filtration-reabsorption theory. Direct sampling of the fluid in nephrons with fine glass tubes (micropuncture) by Alfred Richards in the 1920s and 1930s proved that the capsule contains an ultrafiltrate of plasma. The countercurrent mechanism was clarified in the 1950s by Werner Kuhn and Bodil Schmidt-Nielsen and others.

Which mistakes are common?

Mistake 1: Saying that the kidney filters by size only in the tubule

Filtration occurs at the glomerulus. The tubule reabsorbs.

Mistake 2: Thinking that filtration removes only waste

Useful substances such as glucose and amino acids are filtered too, and are reabsorbed afterward.

Mistake 3: Forgetting the blood pressure

High pressure in the glomerulus, due to the narrower efferent arteriole, drives filtration.

Mistake 4: Confusing the ureter and the urethra

The ureter carries urine from the kidney to the bladder. The urethra carries it from the bladder out of the body.