BS1060 - Renal Physiology - Part 2 (Dr Vial)

Overview

• This document discusses renal physiology focusing on the medulla's vertical osmotic gradient and how it influences urine concentration.

Course Information

• Source: Modified from Sherwood, L. (2004) Human Physiology From Cells to Systems. 5th Ed. Brooks/Cole –Thomson Learning, Belmont CA, USA.

• Instructor: Catherine Vial (cv12@le.ac.uk)

• University: University of Leicester

• Course Code: BS1060 - Renal Physiology Part 2

Intended Learning Outcomes

By the end of the session, students should be able to:

• Define the role of the vertical osmotic gradient in controlling urine concentration.

• Describe how the vertical osmotic gradient is established and maintained.

• Explain the role of vasopressin in urine concentration modulation.

• Detail factors that can disrupt vasopressin function (e.g., alcohol consumption, nephrogenic diabetes insipidus).

• Discuss factors influencing the strength of the vertical osmotic gradient.

Vertical Osmotic Gradient in the Renal Medulla

• Enables kidney production of urine ranging in concentration from 100 to 1200 mosm/L.

• Influenced by:

  • Body hydration state

  • ECF solute concentration

  • Arterial blood pressure

Establishment of the Medullary Vertical Osmotic Gradient

• Juxtamedullary Nephrons:

  • Long loops of Henle (LoH) are responsible for establishing the gradient.

  • LoH enables a concentration of urine, comparison of frogs (which lack LoH) and mammals (which have LoH).

• Historical Contributions:

  • Mid-1920s: Marian M. Crane's speculation about concentration due to LoH.

  • 1958-59: Margaret Mylle et al. presented first direct measurement of osmolality in various LoH sections.

Mechanism of the Loop of Henle

• Descending Limb: Permeable to water, leading to water diffusion and osmotic gradient.

• Ascending Limb: Impermeable to water; Na+ and Cl- exit causing decreasing osmolarity in the tubule lumen and increasing osmolarity in interstitial fluid, enhancing the gradient.

• Active transport: Na+/K+-ATPase in tubular cells facilitates Na+ movement into the interstitial fluid.

Countercurrent Mechanism

• Fluid flows in opposite directions in descending and ascending limbs of the LoH, magnifying osmotic pressure.

• This process termed Countercurrent Multiplication.

Function of the Vasa Recta

• Peritubular capillaries that flow opposite to urine, allowing gas exchange and nutrient reabsorption.

• Stabilize the osmotic gradient by equilibrating with the interstitial fluid.

Role of Vasopressin (ADH)

• Hormone involved in the reabsorption of water in distal tubules and collecting ducts in response to hydration states.

• Mechanism:

  • Binds to receptors on distal tubular and collecting duct cells, inducing relocation of aquaporins to apical membrane.

  • Increases water reabsorption, concentrating urine above 100 mosm/L.

Urine Concentration Regulation

• Healthy Hydration:

  • 1.25 ml/min of isotonic urine formation (300 mosm/L).

  • Excess water results in dilute urine formation (as low as 100 mosm/L).

• Dehydration:

  • Leads to concentrated urine formation (up to 1200 mosm/L) as vasopressin secretion increases.

Disruption of Vasopressin Function

• Alcohol: Inhibits vasopressin release, causing dilute urine and increased urination.

• Nephrogenic Diabetes Insipidus:

  • Conditions where distal tubules and collecting ducts fail to respond to vasopressin, leading to excessive dilute urine (polyuria), dehydration, and thirst.

  • Health risks if untreated.

Comparative Analysis

• Nephron Comparison:

  • Longer nephrons deepen osmotic gradient, enabling more concentrated urine formation in adapted species, such as the kangaroo rat.