ADH and the control of osmolality

ADH and Control of Osmolality Notes

Learning Outcomes

• Define osmolality, osmolarity, hypoosmotic, isoosmotic, and hyperosmotic.

• Explain the countercurrent multiplier system in the loop of Henle and its role in creating a hyperosmotic interstitium in the kidney medulla.

• Describe how the kidney handles urea and how urea trapping contributes to the hyperosmotic interstitium.

• Explain the importance of the structure of the vasa recta.

• Describe ADH secretion in response to changes in plasma osmolality.

• Explain the role of ADH/aquaporins in the collecting duct.

• Explain the production of hyperosmotic (concentrated) and hypoosmotic (dilute) urine, incorporating the above learning outcomes.

Key Concepts

• Water in the Body:

  • Adult human body is approximately 60% water.

  • Two properties under physiological control:

    • Volume (regulated by blood pressure, baroreceptors, renin-angiotensin-aldosterone system).

    • Osmolality (must be maintained for optimal function).

• Osmolality vs. Osmolarity:

  • Osmolality: osmoles per kilogram of water.

  • Osmolarity: osmoles per liter of water.

  • Osmolality is usually preferred in clinical settings, but the terms are often used interchangeably.

  • Example: plasma osmolality is often given as $300 \, \text{mOsmol/L}$ or mOsm/kg.

• Relative Osmolality Terms:

  • Isoosmotic (isotonic): The same osmolality as another solution (e.g., $290 \, \text{mOsmol/kg}$ is isoosmotic to plasma).

  • Hypoosmotic (hypotonic): Lower osmolality than another solution (e.g., $100 \, \text{mOsmol/kg}$ is hyposmotic to plasma).

  • Hyperosmotic (hypertonic): Higher osmolality than another solution (e.g., $400 \, \text{mOsmol/kg}$ is hyperosmotic to plasma).

• Effects of Changes in Extracellular Osmolality

  • If a cell is placed in a:

    • Isoosmotic solution: no change in cell volume.

    • Hypoosmotic solution: water enters the cell, causing it to swell.

    • Hyperosmotic solution: water leaves the cell, causing it to shrink.

Kidney Revision

• Nephron Structure: Macula densa, juxtamedullary nephron, peritubular capillaries, efferent arteriole, afferent arteriole, corticomedullary junction.

• Two types of nephrons: cortical and juxtamedullary.

• Section through cortex of the kidney: proximal convoluted tubule, distal convoluted tubule and Loop of Henle in between

Proximal Convoluted Tubule: Site for regulation of absorption

Distal Convoluted Tubule: Bulk of reabsorption happens, absorb salt & water

Loop of Henle and Osmotic Gradient

• Vertebrate Kidney Systems:

  • Mammalia and Aves: Have a loop of Henle and kidneys subdivided into cortex and medulla.

  • Reptilia, Amphibia, Agnatha, Osteichthyes, Chondrichthyes: No loop of Henle and/or kidney not subdivided. The loop of Henle is essential for concentrating urine and controlling osmolality.

• Osmotic Homeostasis Requirements:

  • The body produces waste that must be excreted in urine.

  • Minimum daily urine production (obligatory water loss) is ~$450 \, \text{mL}$.

  • To control osmolality, kidneys must produce urine ranging from hypoosmotic to hyperosmotic.

  • Water reabsorption must be passive (osmosis) due to high energy demand of active transport.

  • A hyperosmotic region is required to reabsorb water.

• Ascending Limb:

  • Actively reabsorbs solute (Na+, Cl-) into the medullary interstitium.

  • Impermeable to water.

• Descending Limb:

  • Freely permeable to water via aquaporins.

  • Water passively reabsorbed into the medullary interstitium.

  • Not permeable to solute.

• Osmolality Changes in the Loop:

  • Filtrate entering the loop of Henle is isoosmotic to plasma (~$290 \, \text{mOsmol/kg}$).

  • In the ascending limb, the filtrate becomes hypoosmotic to plasma (~$100 \, \text{mOsmol/kg}$).

  • In the descending limb, the filtrate becomes hyperosmotic to plasma (~$1200 \, \text{mOsmol/kg}$).

• Countercurrent Multiplier:

  • The loop of Henle creates an osmotic gradient in the medullary interstitium.

  • Water is reabsorbed in the descending limb until equilibrium is reached between the filtrate and the medullary interstitium.

  • The medullary interstitium becomes progressively hyperosmotic.

• Countercurrent Multiplier Mechanism:

  • Creation of a hyperosmotic medullary interstitium by the loop of Henle.

  • Key is the counterpermeability.

Urea Trapping

• Urea freely filtered in the glomerulus.

• $50\%$ of filtered urea is reabsorbed in the proximal convoluted tubule.

• $30\%$ of filtered urea is reabsorbed in the distal convoluted tubule and cortical collecting duct.

• Remaining urea is trapped in the medullary interstitium and contributes to its hyperosmotic state.

• About $50\%$ of filtered urea is secreted by passive diffusion into the Loop of Henle.

• $55\%$ of filtered urea is reabsorbed in the medullary collecting duct.

• $5\%$ of filtered urea is reabsorbed into the medullary capillary system (vasa recta).

• $15\%$ of filtered urea is excreted in the urine.

Vasa Recta

• The medullary capillary system (vasa recta) maintains the hyperosmotic medullary interstitium.

• Blood flow passing directly through the interstitium would wash away the osmotic gradient.

• The vasa recta consists of straight loops.

• Plasma osmolality in the vasa recta equilibrates with the interstitium.

• Solute and water reabsorbed by the loop of Henle are removed in equal proportion, maintaining the osmotic gradient.

Urine Production and ADH

• Hypoosmotic Urine Production:

  • The medullary collecting duct is not very permeable to water.

  • Hypoosmotic filtrate flows down the collecting duct and is released as hypoosmotic urine.

• Hyperosmotic Urine Production:

  • Aquaporins are inserted into the membranes of the medullary collecting duct.

  • The collecting duct becomes more permeable to water.

  • Water is reabsorbed into the hyperosmotic interstitium.

  • The filtrate becomes hyperosmotic as it flows down the collecting duct.

• ADH and Aquaporins:

  • Antidiuretic hormone (ADH) causes the insertion of aquaporins into the collecting duct membranes.

  • ADH, also known as vasopressin or arginine vasopressin, is a peptide hormone.

  • ADH binds to V2 receptors on medullary collecting duct cell membranes.

  • The V2 receptor is a G protein-coupled receptor.

  • Signaling cascade leads to insertion of aquaporins.

  • Insertion of aquaporins leads to absorption of water into the hyperosmotic interstitium.

• ADH Release:

  • ADH is released into the blood by the posterior pituitary.

  • Synthesized by neurons in the supraoptic and paraventricular nuclei of the hypothalamus.

  • Released by these neurons into capillaries of the posterior pituitary, from where it enters the general circulation.

• Control of ADH Release:

  • ADH release is controlled by osmoreceptors.

  • Neurons in the supraoptic and paraventricular nuclei receive input from central osmoreceptors.

  • These osmoreceptors detect changes in plasma osmolality.

  • Increased plasma osmolality decreases (↓) the rate of ADH secretion

  • Decreased plasma osmolality increases (+) the rate of ADH secretion

  • In situations of large fluid loss (e.g., hemorrhage), ADH secretion can be stimulated by baroreceptors to promote conservation of water.

• Summary of Response to Increased Plasma Osmolality:

  • Increased Plasma osmolality

  • Osmoreceptor activation (+)

  • ADH secretion from hypothalamus/posterior pituitary (+)

  • Increased plasma ADH

  • Increased permeability of collecting ducts in kidney (+)

  • Increased H₂O reabsorption (+)

  • Decreased H₂O excretion

  • Ingestion of H₂O (+)

  • Thirst (+)

Question

• Diabetes insipidus is caused by an inability to produce or respond to ADH (e.g., a mutation in the V2 receptor).

• Symptom: Overproduction of urine.

• Note: Not the same as Diabetes mellitus (sugar diabetes).