Lecture 25- Regulation of acid base mechanism.pptx

Renal

1. Lect 25: Renal Regulation Human Physiology II

2. Learning Objectives Describe activation and factors of RAA Describe the consequences of sympathetic stimulation, ANG II, aldosterone, and ANP

3. Control of ECF Volume & Osmolarity Body volume is largely controlled by regulating Na reabsorption. Body osmolarity is largely controlled by regulating water reabsorption. Main osmotic constituents of ECF is Na+ & Cl-. ↑[Na+] plasma ⇒ ↑ plasma osmolality ⇒ ↑ ADH. ↑[Na+] plasma ⇒ ↑ ECF ⇒ ↑ Na+ excretion ↓[Na+] plasma ⇒ ↓ ECF ⇒ ↓ Na+ excretion Note: The signal triggering regulation of Na+ excretion is not [Na] plasma , rather, it’s the altered ECF volume.

4. Feedback Control of ECF Volume Sensors: baroreceptors. Hormonal response: RAAs (renin- angiotensin-aldosterone system), sympathetics, ADH & ANP. Consequence: change in renal Na + reabsorption to counteract ECF change

5. Activation of RAAs ↓ECF circulating ⇒ ↓GFR ⇒ ↓NaCl - delivery to macula densa ⇒ ↑Renin ⇒ angiotensinogen conversion to ANG I ⇒ ANG I to ANG II (catalyzed by ACE). The trigger is ↓ [Ca 2+ ] intracellular in granular cells of JGA due to reduce stretch. Renin secretion also induced by ↑sympathetic tone due to ↓GFR. This is mediated by β 2 receptors on granular cells of JGA. Note TGF feedback results in afferent contraction when ↑GFR and induces renin release when ↓GFR. ANG II stimulate thirst, AVP & aldosterone resulting in ↑H 2 O intake, ↓H 2 O excretion & ↓Na+ excretion ⇒ ↑ECF

6. Renal Consequences of ↑RAA: ANG II Why is filtration fraction increased? The combined vasoconstriction of afferent and efferent arteriols reduces RBF significanly . But, because efferent vasoconstriction is higher, the backpressure results in a smaller reduction of GFR as compared to RBF. Thus ↑FF. This results in a higher oncotic pressure in the peritubular capillaries. Because RBF is reduced, hydrostatic pressure in peritubular capillaries is lower. Consequently, filtration pressure in those capillaries is lower, that is more water and salts are absorbed. Why is [Na + ] decreased in medulla? Vasa recta blood flow decreased because upstream vasoconstriction. Washout of medullary urea is reduced further from normal. More water reabsorbed in response to higher [urea] and this dilutes [Na + ] resulting in a higher transepithelial Na+ gradient which leads to higher paracellular reabsorption in the tALH .

7. Renal Consequences of ↑RAA: Aldosterone ↑aldosterone⇒↑ENaC in principal cells of collecting tubules⇒↑Na + reabsorption ↑aldosterone⇒↑Na/K pump Recall that there are also K channels in the principal cells (not shown) and the increase of Na reabsorption leads to a more negative lumen which draws more K into the lumen.

8. Renal Consequences of ANP Pressure receptors in atrium release atrial natriuretic peptide (ANP) in response to stretch ↓ECF circulating ⇒↓pressure⇒↓ANP ↑ECF circulating ⇒↑pressure ⇒↑ANP ⇒↑↑RBF due to vasodilation ⇒ ↑GFR ⇒ ↑Na+ load delivered to distal segments ⇒ ↑natriuresis ↑ANP ⇒↓Na channel in MCD ⇒ ↓Na reabsorption ⇒ ↑natriuresis

9. Summary ECF volume is controlled by regulating Na reabsorption. RAA affects level of Na reabsorption. Reduction in GFR due to reduction in ECF volume induces renin secretion and thus angiotensin II. Angiotensin II changes hemodynamics of the peritubular capillaries and vasa recta resulting in greater PT reabsorption of Na. Angiotensin II induces aldosterone release which increases Na reabsorption by principal cells. ANP result in greater Na excretion.