0811- body volume regulation- CG

Question 1

Aims

Answer 1

At the end of this lecture students should be able to • recognise why osmo- is different to volume-control; • explain how ADH controls osmolality; • identify factors that control and modulate ADH secretion; • outline the role of thirst in fluid homeostasis; • recognise “effective circulating volume” and how the body measures it; • locate volume control elements (renin-angiotensinaldosterone (RAA) system, etc.); • illustrate how tubular reabsorption rates are altered in hypo- and hypervolumic states; and • discuss the hierarchy in homeostatic osmo- and volumecontrol.

Question 2

Compare osmolality control and volume control

Answer 2

Fluid osmolality: H2O excretion/retention (ADH) Fluid volume: NaCl excretion/retention (RAA) Both ECF parameters depend on each other (ie ADH secretion is indirectly modulated via ang 2)

Question 3

How does ADH control osmolality?

Answer 3

• ADH is synthesised in hypothalamus as prohormone. - Released via posterior pituitary. - AP mediated, phasic secretion (pulsatile) ADH inserts aquaporins to apical membrane in DT/CD, increasing reabsorption of H2O and diluting (decreasing) osmolality Other effects: - Increase urea diffusion via urea transporters - Effect on gene expression long term

Question 4

Describe factors that modulate ADH secretion

Answer 4

• ADH secreted when ~1% increase in effective osmolarity (normal range 280-295 mOsm) - Changes in BP (via cardiopulmonary receptors and arterial receptors) Osmolarity increases when HYPOVOLEMIC and HYPOTENSIVE.

Question 5

• outline the role of thirst in fluid homeostasis;

Answer 5

• triggered by 2-3% rise in osmolality • ADH and thirst in tandem regulate osmolality: conservation of H2O and drinking, respectively. Satiation response (ie thirst) faster than plasma correction (ie ADH)

Question 6

recognise “effective circulating volume” and how the body measures it;

Answer 6

Effective circulating volume (CVe) = = fluid contained within vascular system AND effectively perfusing tissues (related to Na+ balance by kidney, influenced by BP and CO) • Effective perfusion↓ → Na+ retention → ECF↑ (extravasation of fluid does not count as CVe- ie oedema, shunts, etc)

Question 7

• locate volume control elements (renin-angiotensinaldosterone (RAA) system, etc.);

Answer 7

Targets NaCl reabsorption rates along renal tubule Local (confined to single nephron): Glomerulo-vascular regulation (TGF) 1.Autoregulation of perfusion via angiotensin II- afferent arteriole constriction: GFR↓ and RBF↓. 2. Macula densa chemoreceptors- [NaCl] ↑ → GFR ↓ via afferent arteriole constriction Can be overwritten by systemic response. Systemic: Systemic control of volume & BP – Slow response Different elements and targets involved, mediated by nerves and multiple hormones. 1. Neural: Renal sympathetic nerve stimulation • Vascular α-response: GFR↓. • PT response: NaCl reabsorption↑ 2. Juxtoglomerular cells (PT)- secrete renin in response to BP (SYSTEMIC) 3. Hormones- RAAS activation •Angiotension 2 •Aldosterone Both ↑ NaCl reabsorption (H2O retention), ↓ K+ secretion •Urodilatin: locally acting hormone in kidney, ANP

Question 8

• illustrate how tubular reabsorption rates are altered in hypo- and hypervolumic states; and

Answer 8

Volume expansion response- net NaCl loss Initial Response (fast) - ↑ Sympathetic activity - ↑ANP, ↓ADH - ↓RAAS Volume contraction response- net Na retention with K+ loss - ↓Sympathetic activity - ↓ANP, ↑ADH - ↑RAAS

Question 9

• discuss the hierarchy in homeostatic osmo- and volumecontrol.

Answer 9

Osmocontrol prevails over volume control (strong and faster response) Hence tendency to drink more water, not salt