Nephron: Kidney Structure, Function, and Regulation

Posted on Aug 25, 2025 in Medicine

The nephron is the functional unit of the kidney. Each kidney contains approximately 1 million nephrons, which do not regenerate if destroyed. From age 40, approximately 1% of nephrons are lost each year.

Components of the Nephron

The nephron is primarily formed by the glomerulus and the tubular system.

Glomerulus

An afferent arteriole, originating from the renal artery, reaches the glomerulus and branches into glomerular capillaries. These capillaries are highly permeable—approximately 400 times more permeable than capillaries in the rest of the body.

Glomerular Capillary Structure

• Endothelium
• Basement Membrane
• Podocytes

Bowman’s Capsule

Composed of squamous epithelial cells, Bowman’s capsule lines the capillaries and collects the filtrate from them, channeling it into the tubular system.

General Functions of the Kidney

The kidneys perform several vital functions:

• Regulation of Fluid and Electrolyte Balance: This depends significantly on dietary intake, as the kidney must constantly adjust to maintain homeostatic equilibrium.
• Excretion of Metabolic Waste Products: Essential for removing harmful substances, as many enzymes are sensitive to changes in pH.
• pH Regulation: Maintaining the body’s acid-base balance.
• Blood Pressure Regulation: Through various mechanisms, including renin secretion.
• Influence on Red Blood Cell Formation: Production of Erythropoietin (EPO).
• Regulation of Vitamin D Formation: Activating Vitamin D to its active form.

Segments of the Nephron and Their Functions

1. Proximal Convoluted Tubule (PCT)

The longest portion of the nephron, the PCT is composed of large cells rich in mitochondria. The apical border features a prominent brush border with numerous ion channels. Many Na⁺/K⁺ pumps create an intracellular Na⁺ deficit, causing Na⁺ to move from the tubular lumen into the cells. Through countertransport mechanisms, 100% of filtered glucose and amino acids are reabsorbed here. Additionally, approximately 65% of Na⁺, Cl^–, HCO₃^–, and K⁺ are reabsorbed.

Note: Complete reabsorption of amino acids and glucose may not occur under certain conditions, such as diabetes.

2. Descending Limb of the Loop of Henle

Characterized by a thin epithelium, these cells are very thin, poor in mitochondria, and lack Na⁺/K⁺ pumps. These cells are highly permeable to water.

3. Ascending Limb of the Loop of Henle

This segment features a thick epithelium with large cells rich in mitochondria and Na⁺/K⁺ pumps. Approximately 25% of Na⁺, Cl^–, and K⁺ are reabsorbed here, along with variable amounts of Ca²⁺, Mg²⁺, and HCO₃^–. A specific countertransport mechanism in this area allows one Na⁺ ion to enter along with two Cl^– ions and one K⁺ ion, contributing to reduced osmolarity. The cells are completely impermeable to water due to glycoprotein coverage that waterproofs the cells and strong intercellular anchoring mechanisms (tight junctions).

4. Distal Convoluted Tubule (DCT)

The proximal portion of the DCT resembles the thick ascending limb of Henle’s loop. The distal portion resembles the collecting duct.

5. Collecting Duct

The collecting duct contains two primary types of cells:

• Principal Cells (most abundant): These are fairly large cells with some capacity to pump Na⁺/K⁺. Their ability to reabsorb solutes is largely mediated by aldosterone, which stimulates the cell nucleus to increase the synthesis of Na⁺/K⁺ pumps. Unlike other body cells, their water permeability is variable, regulated by aquaporin II channels. They are also able to secrete K⁺. Atrial Natriuretic Peptide (ANP), secreted in the right atrium due to increased atrial filling, inhibits ion channels, reducing Na⁺ reabsorption and increasing its elimination, thereby lowering blood pressure.
• Intercalated Cells: Located in the cortical portion of the collecting duct. They are dedicated to reabsorbing K⁺ and HCO₃^– and secreting H⁺, thus playing a crucial role in pH regulation.

Renal Autoregulation Mechanisms

This autonomous mechanism maintains a constant glomerular filtration rate (GFR) despite fluctuations in blood pressure (typically between 70 and 160 mmHg).

Tubuloglomerular Feedback

In response to decreased blood pressure, the glomerular filtration rate tends to decrease, resulting in lower intratubular fluid flow. In the distal tubule, macula densa cells are sensitive to sodium chloride concentration (which is proportional to the filtration rate). These activated macula densa cells produce two phenomena:

• Vasodilation in afferent arterioles
• Activation of juxtaglomerular cells

Myogenic Effect

In response to increased blood pressure, the afferent arterioles constrict, reducing blood flow to the glomerulus and helping to maintain a stable GFR. This effect also involves the activation of juxtaglomerular cells.

General Metabolic Functions (Contextual Information)

This section provides general metabolic information, often associated with liver function, for broader biological context.

• Carbohydrate Metabolism:
  • Glycogen storage.
  • Conversion of galactose into glucose and fructose.
  • Gluconeogenesis.
• Fat Metabolism:
  • Fatty acid oxidation.
  • Formation of lipoproteins.
  • Cholesterol and phospholipid synthesis.
  • Transformation of carbohydrates into fat.
• Protein Metabolism:
  • Deamination of amino acids (urea formation).
  • Formation of plasma proteins (except gamma-globulins).
  • Production of non-essential amino acids.
• Other Metabolic Functions:
  • Storage of vitamins A, D, and B12.
  • Importance in clotting mechanisms (plasma proteins).
  • Storage of iron as ferritin.
  • Elimination of drugs.
  • Calcium excretion via bile.