Proximal Convoluted Tubule

1. Overview

The Proximal Convoluted Tubule (PCT) is the first segment of the renal tubule following the glomerulus in each nephron. It plays a critical role in reabsorbing the majority of filtered water, ions, glucose, and nutrients from the glomerular filtrate. The PCT is where most of the reabsorption in the nephron occurs, making it essential for maintaining the body's fluid, electrolyte, and nutrient balance.

2. Location

The PCT is located in the renal cortex, beginning at the Bowman’s capsule, where it receives the filtrate produced by the glomerulus. It is the first tubular segment of the nephron and lies near the renal corpuscle. After winding through the cortex in a highly coiled path, the PCT transitions into the loop of Henle as it enters the renal medulla.

3. Structure

The PCT is composed of a simple cuboidal epithelium with specialized features that maximize its reabsorptive capacity:

• Brush border: The apical surface has dense microvilli, dramatically increasing surface area for absorption.

• Mitochondria-rich cytoplasm: The epithelial cells contain numerous mitochondria to support active transport processes.

• Basolateral infoldings: Facilitate transport of reabsorbed substances into surrounding peritubular capillaries.

• Tight junctions: Permit selective paracellular movement of certain ions while maintaining tubular integrity.

4. Function

The Proximal Convoluted Tubule reclaims approximately 65–70% of the filtrate volume. Key reabsorptive and secretory functions include:

• Water reabsorption: Follows solute reabsorption via osmosis (isotonic).

• Electrolyte reabsorption: Reclaims Na⁺, K⁺, Cl⁻, HCO₃⁻, Ca²⁺, and phosphate.

• Glucose and amino acid reabsorption: Nearly 100% reabsorbed via sodium-coupled co-transporters.

• Secretion of waste products: Actively secretes creatinine, drugs (e.g., penicillin), and toxins into the tubule for excretion.

5. Physiological Role(s)

The PCT is involved in multiple key physiological processes:

• Volume regulation: Maintains extracellular fluid volume by reabsorbing sodium and water.

• Acid-base balance: Reabsorbs bicarbonate and secretes hydrogen ions to regulate pH.

• Glucose homeostasis: Prevents loss of glucose in urine under normal physiological conditions.

• Tubular maximum (Tm): Has a finite capacity to reabsorb substances like glucose—beyond which they appear in urine (e.g., glycosuria).

6. Clinical Significance

Acute Tubular Necrosis (ATN)

The PCT is highly susceptible to ischemic and nephrotoxic injury due to its high metabolic activity. ATN is the most common cause of acute kidney injury and may result from:

• Hypotension or shock

• Aminoglycoside antibiotics

• Radiocontrast agents

Pathological findings include loss of brush border and cell necrosis.

Fanconi Syndrome

A disorder of proximal tubular function leading to impaired reabsorption of glucose, amino acids, phosphate, and bicarbonate. Causes include:

• Genetic disorders (e.g., cystinosis)

• Drug toxicity (e.g., ifosfamide, tenofovir)

• Heavy metal exposure (e.g., lead, cadmium)

Symptoms include polyuria, hypophosphatemia, and metabolic acidosis.

Glycosuria in Diabetes Mellitus

When blood glucose exceeds the renal threshold (~180 mg/dL), the PCT’s glucose transporters are saturated, resulting in glucose spilling into the urine, a hallmark of uncontrolled diabetes.

Proximal Renal Tubular Acidosis (Type II RTA)

Defect in bicarbonate reabsorption in the PCT causes metabolic acidosis. It may be inherited or acquired (e.g., due to drugs like acetazolamide).

Drug Handling

Many medications are secreted or reabsorbed in the PCT. Examples include:

• Diuretics (e.g., acetazolamide—carbonic anhydrase inhibitor)

• Penicillins (secreted actively via transporters)

• NSAIDs (can reduce renal perfusion and affect PCT function)

Imaging and Biopsy

Though not visible directly on imaging, PCT injury is often inferred in renal biopsies via:

• Loss of brush border

• Tubular cell flattening

• Granular casts in tubules (especially in ATN)