Loop of Henle

1. Overview

The Loop of Henle is a U-shaped portion of the nephron that extends into the renal medulla and plays a key role in concentrating urine. It connects the proximal convoluted tubule to the distal convoluted tubule and enables the kidney to produce urine that is more concentrated than plasma, a vital process for water conservation and electrolyte balance. Named after German anatomist Friedrich Gustav Jakob Henle, this structure is fundamental to the kidney’s countercurrent mechanism.

2. Location

The Loop of Henle spans both the renal cortex and renal medulla:

• It begins in the cortex, where it continues from the proximal tubule.

• It dips into the outer and inner medulla, forming a loop, and then returns to the cortex to connect with the distal convoluted tubule.

• In cortical nephrons, the loop is shorter and stays mostly in the outer medulla.

• In juxtamedullary nephrons, the loop is longer and penetrates deep into the inner medulla, contributing significantly to the concentration gradient in the kidney.

3. Structure

The Loop of Henle consists of three main segments:

• Thin Descending Limb:

  • Permeable to water

  • Impermeable to solutes (Na⁺, Cl⁻)

  • Composed of simple squamous epithelium

• Thin Ascending Limb:

  • Impermeable to water

  • Allows passive diffusion of Na⁺ and Cl⁻

  • Also lined by simple squamous epithelium

• Thick Ascending Limb:

  • Actively transports Na⁺, K⁺, and Cl⁻ via the NKCC2 cotransporter

  • Impermeable to water

  • Composed of cuboidal or low columnar epithelial cells with abundant mitochondria

This combination of water-permeable and impermeable segments is essential for the countercurrent multiplication mechanism.

4. Function

The main function of the Loop of Henle is to create a hyperosmotic medullary interstitium, which enables the kidney to concentrate urine and conserve water. Key functions include:

• Water reabsorption: Occurs in the thin descending limb.

• Solute reabsorption: Occurs in the thick ascending limb (active Na⁺, K⁺, Cl⁻ transport).

• Establishing the corticomedullary osmotic gradient: Essential for water reabsorption in the collecting duct under ADH influence.

5. Physiological Role(s)

The Loop of Henle plays a vital role in renal physiology and systemic balance:

• Countercurrent multiplication: Creates a gradient that enables water reabsorption from the collecting ducts, crucial for forming concentrated urine.

• Conservation of body fluids: Helps prevent dehydration by reducing water loss.

• Electrolyte balance: Reabsorbs significant amounts of filtered sodium, chloride, and potassium.

• Facilitates urea recycling: Assists in maintaining high medullary osmolality, especially in juxtamedullary nephrons.

6. Clinical Significance

Diuretic Action

The thick ascending limb is the target of loop diuretics (e.g., furosemide, bumetanide), which inhibit the NKCC2 transporter. This results in:

• Increased excretion of Na⁺, K⁺, Cl⁻

• Reduced medullary concentration gradient

• Increased urine output (potent diuresis)

Bartter Syndrome

A group of rare genetic disorders involving mutations in transport proteins of the thick ascending limb. Features include:

• Hypokalemia

• Metabolic alkalosis

• Salt wasting

• Hyperreninemia and hyperaldosteronism (without hypertension)

Ischemic Injury

The thick ascending limb is highly metabolically active and susceptible to ischemic acute tubular necrosis (ATN). This can occur during:

• Hypotension

• Sepsis

• Nephrotoxic drug exposure

Leads to impaired sodium handling and decreased urine concentration ability.

Concentrating Defects

In diseases affecting the Loop of Henle or medullary architecture (e.g., interstitial nephritis, sickle cell disease), the ability to concentrate urine is impaired, leading to polyuria and nocturia.

Imaging and Biopsy

Although difficult to visualize directly on imaging, damage to structures involving the Loop of Henle may be inferred through biopsy or functional testing (e.g., concentrating ability). Histological signs include:

• Loss of epithelial integrity

• Flattening of tubular cells

• Cell sloughing and tubular obstruction