Regulation of Homeostasis by kidney - fluid balance Flashcards
ADH
Collecting duct permeability increased by ADH
Non peptide with Mw of just over 1000; also known as vasopressin
Plasma half-life 10-15 mins
ADH acts on V2 receptors on basal membrane of principal cells in collecting duct
Leads to insertion of aquaporin 2 water channels into apical surface
Max ADH = concentrated urine
Volume regulation by ADH
ADH released in response to changes in plasma osmolality and effective circulating volume (ECV)
These changes are detected by osmoreceptors and baroreceptors
Consider dehydration:
- Increased plasma osmolality stimulates osmoreceptors in the hypothalamus which trigger ADH release
- Result: more water reabsorbed from collecting ducts in kidney back into circulation. This leads to increased ECV
- Increased osmolality also stimulates a second group of osmoreceptors in the hypothalamus which trigger thirst
- Result: promotes water intake which enters circulation. This also increases ECV
Countercurrent multiplication
Active transport of NaCl contributes 600-1000 mOsm - the remainder is due to urea
Urea freely filtered at glomerulus, some reabsorption in proximal tubule, but LOH and distal tubule relatively impermeable to urea
Urea can diffuse out of collecting duct into medulla down its concentration gradient
This adds to the osmolality of medullary interstitium
Baroreceptors
Detect changes in ECV
Central vascular sensors:
- Low pressure blood volume receptors (v important) - large systemic veins, cardiac atria, pulmonary vasculature
- High pressure arterial stretch receptors (less important) - carotid sinus, aortic arch, renal afferent arteriole
Sensors in the CNS and liver
Control of effective circulating volume
Feedback control of ECV exists - mediated by baroreceptor stimulation
Changes in ECV trigger: RAAS, sympathetic NS, ADH release, ANP release
Together these change renal haemodynamics and Na+ transport by renal tubule cells
Renin-Angiotensin-Aldosterone System
Principal factor controlling plasma Ang II levels: renin release from JGA
Decreased ECV stimulates renin release via:
- Decreased renal perfusion pressure detected in the afferent arteriole - the “renal baroreceptor”
- Decreased Na+ concentration in distal tubule detected by the macula densa cells - the “renal Na+ sensor”
- Decreased systemic BP also triggers effects of the sympathetic nervous system supplying the JGA
Important actions of Ang II
(1) Enhances tubular Na+ transport in the kidney - this promotes Na+ and water reabsorption from tubule
(2) Stimulation of aldosterone release from adrenal cortex - so more Na+ and water is reabsorbed from distal tubule/collecting duct
(3) Acts on the hypothalamus to stimulate thirst and ADH release into circulation - water intake adds to ECV & ADH increases water reabsorption from the collecting duct
All the actions of Ang II actions are designed to increase ECV
ALSO, vasoconstriction of renal and other systemic vessels (BP increases); Ang II causes renal cell hypertrophy, so more protein synthesis of Na+ transporters and channels
Important actions of aldosterone
Stimulates Na+ reabsorption (and K+ excretion) in the distal tubule and collecting duct
Aldosterone also exerts indirect negative feedback on the RAAS by increasing ECV and by lowering plasma K+ concentrations
Important in conserving Na+ and water, but also important in preventing large variation in plasma K+ levels (by causing its excretion out of the kidney)
Volume regulation pathway 1 - RAAS
Decreased ECV -> detected by renal baroreceptors and renal Na+ sensors -> activation of RAAS -> reduced Na+ excretion by kidney, increased renal Na+ reabsorption -> increased ECV
Volume regulation pathway 2 - ANS
Decreased ECV -> detected by peripheral baroreceptors -> signals to hypothalamus -> reduced Na+ excretion and increased renal Na+ absorption (due to direct effects on renal haemodynamics and activation of RAAS) -> increased ECV
Volume regulation pathway 3 - ADH
Decreased ECV -> peripheral baroreceptors -> signals to hypothalamus -> release of ADH -> increased water reabsorption in kidney -> increased ECV
Atrial Natiuretic Peptide (ANP)
ANP is designed to lower ECV
Atrial myocytes synthesise and store ANP
Increased ECV causes atrial stretch which leads to ANP release into circulation
ANP promotes natriuresis and causes renal vasodilation so increased blood flow (increased GFR so more Na+ excreted)
More Na+ reaches the macula dense so renin release by JGA is reduced - reduces effects of Ang II
Overall effects: inhibit action of renin and opposes effect of Ang II
