Physiology - lecture 15 - ADH and the Control of Osmolality

Learning Outcomes

  • Define Key Terms:

    • Osmolality, osmolarity, hypoosmotic, isoosmotic, hyperosmotic.

  • Countercurrent Multiplier:

    • Explain how the loop of Henle creates hyperosmotic interstitium in kidney medulla.

  • Kidney Functionality:

    • Describe urea handling and 'trapping' effects on medullary osmolality.

  • Vasa Recta Structure Importance:

    • Explain the role of vasa recta in osmotic homeostasis.

  • ADH Secretion:

    • How ADH responds to plasma osmolality changes.

  • Role of ADH and Aquaporins:

    • Detail how ADH regulates urine osmolality at the collecting duct.

Water in the Body

  • Adult human body is approximately 60% water.

  • Key properties of water under physiological control:

    1. Volume Regulation:

      • Refer to lectures on blood pressure/baroreceptors/renin-angiotensin-aldosterone system.

    2. Osmolality Regulation:

      • Optimal function is crucial for processes like action potentials and muscle contraction.

Osmolality Definitions

  • Osmolality:

    • The ability of solutes to lower the concentration of water

    • Defined as osmoles per kilogram of water.

  • Osmolarity:

    • Defined as osmoles per liter of water.

  • Clinical Preference:

    • 'Osmolality' is typically preferred in clinical contexts, although both terms are often used interchangeably.

Relative Osmolality Terms

  • Isoosmotic (Isotonic):

    • Same osmolality as reference solution

  • Hypoosmotic (Hypotonic):

    • Lower osmolality than reference solution

  • Hyperosmotic (Hypertonic):

    • Higher osmolality than reference solution

Effects of Changes in Extracellular Osmolality

  • Isoosmotic Solution:

    • No change to 'cell'; equilibrium maintained.

  • Hypoosmotic Solution:

    • 'Cell' expands due to water influx.

  • Hyperosmotic Solution:

    • 'Cell' shrinks as water exits.

Nephron & Kidney Structure

  • Key Components:

    • Glomerulus, proximal convoluted tubule, distal convoluted tubule, vasa recta, Loop of Henle, collecting ducts.

  • Segments of Nephron:

    • Proximal convoluted tubule is crucial for bulk reabsorption.

      • Contains microvilli

    • Distal convoluted tubule fine-tunes absorption.

    • Loop of Henle: essential to the ability to conserve water and control extracellular osmolality.

Vertebrate Groups and Loop of Henle

  • Mammals and Birds (Aves):

    • Have a Loop of Henle with distinct cortex and medulla.

  • Reptiles and Fish:

    • Lack Loop of Henle; cannot regulate osmolality effectively.

Urine Production and Osmolality

  • Obligatory Water Loss:

    • Minimum urine production is ~450 mL to excrete waste.

  • To control osmolality:

    • Kidneys must produce a range of urine concentrations from hypoosmotic to hyperosmotic.

    • Water reabsorption must be passive (osmosis).

Loop of Henle Function

  • Ascending Limb:

    • Actively reabsorbs solute (Na+, Cl-) and is water-impermeable.

    • Solute is actively reabsorved into the medullary interstitium

  • Descending Limb:

    • Freely permeable to water, allowing passive reabsorption into medullary

    • Water is reabsorbed until equilibrium is reached.

Countercurrent Multiplier Mechanism

  • Osmotic Gradient Creation:

    • Water is reabsorbed from the descending limb, equilibrating with medullary interstitium osmolality.

    • An osmotic gradient is created as the interstitium becomes progressively hyperosmotic.

  • Countercurrent multiplier: Creation of a hyperosmotic medullary interstitium by the loop of Henle

Urea Trapping

  • Role In Osmolality:

    • Urea is reused in medullary interstitium to enhance hyperosmotic conditions.

  • Urea Handling Statistics:

    • 100% filtered, 50% reabsorbed in proximal tubule, 30% reabsorbed in distal convoluted tubule, 5% excreted.

Vasa Recta Functionality

  • Maintaining Osmotic Gradient:

    • Special structure prevents blood flow disturbance of osmotic gradient.

    • Solute and water is reabsorbed by the loop of Henle are removed in equal so osmotic gradient is maintained.

Urine Concentration Processes

  • Hypoosmotic Urine Production:

    • Low permeability to water in collecting ducts leads to hypoosmotic urine.

  • Hyperosmotic Urine Production:

    • ADH increases collecting duct permeability via aquaporins for hyperosmotic urine.

ADH (Antidiuretic Hormone, Vasopressin)

  • Function:

    • Increases water absorption in kidneys by inserting aquaporins into collecting ducts.

  • Release Mechanism:

    • Synthesized in hypothalamus, released from posterior pituitary into blood.

      • By neurons in the supraoptic and paraventricular nuclei of the hypothalamus

      • ADH neurons receive input from central chemoreceptors that detect plasma osmolality changes

    • ADH binds to V2 GPCRs on medullary collecting duct cell membranes leading to a signalling cascade that inserts aquaporins.

Osmoreceptors and ADH Release

  • Detection of Osmolality Changes:

    • Osmoreceptors in hypothalamus control ADH secretion in response to plasma osmolality.

Summary of Response to Increased Plasma Osmolality

  • Increased plasma osmolality triggers:

    • Thirst, ADH secretion, water reabsorption promoting water balance.

Diabetes Insipidus Symptoms

  • Condition Overview:

    • Caused by inability to produce or respond to ADH.

    • Symptoms include excessive urine production due to lack of water reabsorption.