Regulation of Urine

Loop of Henle and Collecting Duct Anatomy

• Anatomical Overview: Understanding the structure of nephron segments helps keep track of their functions.

  • The nephron consists of several segments: Proximal Convoluted Tubule (PCT), Loop of Henle (LOH), Distal Convoluted Tubule (DCT), and Collecting Duct (CD).

  • Each segment has distinct epithelial tissues, affecting permeability and absorption capacities.

  • PCT: Cuboidal, leaky, with microvilli — absorbs 99% of organic nutrients and ~60–70% of water.

  • Thin Limb of LOH: Squamous, tight, permeable to water only, no active transport of ions.

  • Thick Limb of LOH: Cuboidal, tight, pumps ions but impermeable to water.

  • DCT: Cuboidal, tight, regulates selective ion reabsorption.

  • Collecting Duct: Comprises two key cell types - principal cells (no microvilli) and intercalated cells (microvilli).

Reabsorption Principles

• Counter-Current Multiplication: A mechanism in the Loop of Henle to enhance reabsorption.

  • Counter-Current: Tubular fluid in ascending and descending limbs flows in opposite directions.

  • Multiplication: Different limb permeabilities for water/solutes enhance overall solute and water reabsorption.

• Obligatory vs. Facultative Reabsorption:

  • Obligatory: Occurs in the Loop of Henle (thin descending limb is water-permeable, thick ascending limb pumps out solutes).

  • Facultative: Occurs in DCT and CD, regulated by hormones (ADH and aldosterone).

Hormonal Regulation of Reabsorption

• Antidiuretic Hormone (ADH/AVP):

  • Secreted by the posterior pituitary, it increases water reabsorption in DCT/CD.

  • Binds to AVPR2 receptors, activating pathways that add aquaporins (AQP2) to cell membranes, enhancing water permeability.

  • Regulates body fluid osmolarity by promoting water reabsorption, concentrating urine.

• Aldosterone:

  • Secreted in response to volume depletion; targets DCT and CD.

  • Stimulates Na+/K+ ATPase, increasing Na+ reabsorption and K+ excretion, helping to restore plasma volume.

Symptoms and Diagnosis of Diabetes Insipidus (DI)

• Types:

  • Central (Neurogenic): Lack of ADH production due to damage to hypothalamus.

  • Nephrogenic: Renal resistance to ADH due to receptor/transport defects.

• Common Symptoms: Polyuria (excessive urination) and polydipsia (excessive thirst).

  • Diagnosis made through water deprivation tests and vasopressin stimulation tests.

Diuretic Drugs and Their Mechanisms

• Diuretic Definition: Drugs that increase urine production by affecting nephron transporter proteins.

  • Types:

  • Loop Diuretics: Target Na-K-2Cl cotransporter, impacting the Loop of Henle.

  • Thiazide Diuretics: Affect Na-Cl cotransporter in DCT.

  • Potassium-Sparing Diuretics: Target ENaC in the CD, preventing potassium loss during sodium reabsorption.

Summary of Key Principles for Exam

• Understand the anatomy of the nephron segments and their functions.

• Grasp the principles of counter-current multiplication and the implications for reabsorption efficiency.

• Be familiar with hormonal regulation aspects of reabsorption in DCT and CD, particularly through ADH and aldosterone signaling pathways.

• Recognize the types, symptoms, and pathways related to diabetes insipidus.

• Know the classes of diuretics and their mechanisms within the nephron to manage fluid and electrolytes effectively.