Week 2: Hormonal Control of water excretion

Question 1

Explain why the regulation of water transport affects body fluid osmolality.

Answer 1

• body osmolality is regulated by water input and output (ADH)
• ECF volume is regulated by Na+ and Renin-Ang-Ald system
• both are often regulated in concert

Question 2

Summarize path of ADH (AKA antidiuretic hormone, AVP, vasopressin) synthesis,assembly into granules and transport in the neuroendocrine cells that make it, and role of action potential to cause ADH release.

Answer 2

• a precursor protein synthesized on membrane bound ribosomes in hypothalamus cell body (PVN & SON), transported via Golgi derived granules to nerve terminals of posterior pituitary for storage
• processed while being transported to 9 aa peptide
• osmoreceptors in hypothalamus (or baroceptor input) stimulate action potentials in neuroendocrine cells
• depolarization increases in [Ca2+], causes fusion of ADH containing granules with plasma membrane and release of contents

Question 3

Predict how a change in plasma osmolality alters ADH secretion.

Answer 3

• as little as 3 mOsm change causes osmoreceptors to shrink.
• osomoreceptors in OVLT (organum vasculosum laminae terminalis) and SFO (subfornical organ) in brain where lacks BBB, activates the neurons projecting to PVN and SON
• main signal converning ADH release under normal circumstances

Question 4

Predict how a change in atrial stretch receptor activity (volume) alters ADH secretion.

Answer 4

• senses critical loss of blood volume (~10%)

- trigger ADH release

Question 5

Describe renal cellular actions of ADH

Answer 5

1. Renal targets: cells of cortical, medullary collecting ducts, DCT, and thick ascending loop of Henle
2. Receptors: V2 receptors on vasolateral membranes
3. Acitvates Gs of adenylate cyclase–>pka–>influences microtubules, cell [Ca2+], and transporter phosphorylation and trafficking of AQP2 to apical membrane
4. Activates cyclooxygenase pathway for prostaglandin synthesis to counteract and buffer response

Question 6

Difference in V1 and V2 receptors for ADH?

Answer 6

• V2: in the kidney. High affinity receptors, activated at low plasma ADH
• V1: in vasculature. low affinity. Activated at high ADH.

Question 7

Summarize the cellular actions of ADH in CD on water channels culminating inincreased transepithelial water transport.

Answer 7

• ADH increases water and urea permeability
• causes insertion of AQP2 and urea transporters into apical membrane
• ADH stimulates phosphorylation of AQP2 in the recycling vesicles where they are stored and causes them ago associate with tropomyosin, which destabilizes actin barrier (which was preventing AQP2 from moving to luminal membrane)
• water enters cell via AQP2, and leaves cell to blood via AQP3+4 on basolateral side
• results: more concentrated urine and amore dilute plasma
• In TALH and DCT: ADH increases Na absorption via NaK2Cl, NCC, K+ channel

Question 8

Summarize the cellular actions of ADH in vascular cells on water channels culminating in increased contractility

Answer 8

• V1 receptors, only occupied with high ADH
• acitvates phophatidylinositol pathway—>DAG, IP3–> increases [Ca2+] in ICF–>vasoconstriction
• decrease CV system volume to preserve perfusion pressure

Question 9

Describe what stimulates thirst and why it is important.

Answer 9

• needed to correct Posm
  1. hyperosmolarity: increased Posm–>osmoreceptors in SFO and OVLT activate neurons projecting to SON, PVN to stimulate thirst
  2. Volume contraction: fall in arterial blood pressure increases thirst in response to AngII produced locally in brain
  3. System circulating AngII: strong thirst provoking agent can stimulate AngII receptors in the SFO
  4. Gastric sodium loading: detected by sodium receptors in abdominal viscera, before any increase in systemic plasma osmlarity