Volume Regulation Flashcards
The body can’t easily measure the total extracellular water content. What is regulated, rather is the …………… ……………. ……………..
Usually, actual extracellar volume and the effect circulating volume ………… together e.g. ……………. , ………………
In ………….. …………, however, the heart is not appropriately circulating blood, this is detected, so water is ………
effective circulating volume
change, haemorrhage, sweating
heart failure, retained
What is the juxtoglomerular apparatus?
Where is it located?
What is its function?
- the complex of late distal tubile in associated with renal afferent arteriole
- there are granular cells in the afferent arteriole
- thickening of the wall of the early distal tubule, the macula densa
- the aim of the RAAS is to increase the effected circulating volume
Describe the RAAS?
Start at low Na+ in distal tubule
- low Na+ in distal tubule
- macula densa cells detect
- juxtaglomerular (granule) cells secrete renin
- angiontensinogen form liver is converted into angiotensin I
- ACE converts in into angiotensin II in lungs
- aldosterone release from adrenal cortex
- increased Na+ reabsorption by distal tubule and collecting duct
- increased GFR –> negative feedback as Na+ increases in distal tubule
What are the two main physiological triggers for the release of aldosterone?
What is the evidence that aldosterone must have other renal actions?
angiotensin II and hyperkalaemia
- convergance of these signalling pathways means that, were aldosterone alone the only regulator of ATII action on the kindey, K+ and volume regulation could bot be independently regulated
RAAS can be clinically inhibited in four ways in order to control blood pressure: 1. 2. 3. 4.
ACE inhibtors (-pril) AT1 receptor antagonists (-sartans) aldosterone receptor antagonists (spironolactone) renin inhibition (aliskiren)
What drug classes do the following belong to:
- captopril/enalopril
- candesartan/irbesartan
- spironolactone
- aliskiren
ACE inhibtors (-pril) AT1 receptor antagonists (-sartans) aldosterone receptor antagonists (spironolactone) renin inhibition (aliskiren)`
What is the main receptor in the periphery for the effect of angiotensin II?
What is the signalling pathway for this receptor?
Why are drugs here advantageous over ACE inhibitors?
AT1 receptor
coupled to Gq –> IP3/DAG signalling and increased Ca2+ release from intracellular stores for example smooth muscle cells and the granule cells in the juxtaglomerular apparatus
the ‘sartans’ don’t have the SE of a cough like the ACEi’s do
What are the 5 key action of angiotensin to increase circulating volume?
- vasoconstriction
- increase Na+/H+ exchange in the proximal tubule, and hence proximal Na+ and water reabsorption
- increase in aldosterone release from the adrenal cortex, which increases distal Na+ absorption
- causes ADH release
- causes thirst
How does haemorrhage cause the release of renin?
- decreased vascular volume, decreased venous pressure, decrease cardiac filling, decreased CO, decreased circulating volume
- Leads to decreased blood pressure, increased sympathetic activity, increased renin release
- with the decrease in blood pressure; this is sensed by the afferent arteriole, causing a fall in wall tension and causes the release on renin
What are the 3 actions of sympathetic activation to the afferent arteriole?
- vasoconstriction upstream of the granule cells causes a further fall in the pressure sensed by these cells, and hence amplifies the fall in wall pressure generated by a fall in blood pressure
- direct stimulatin of renin release from the granule cells
- affereant arteriole vasoconstriction drops glomerular hydrostatic pressure to the glomerulus and hence lower’s GFR
Which adrenoreceptors are located on the vascular smooth muscle cells and the granule cells and to which G-protein are they coupled?
transmitter = NA
vascular smooth muscle cells = alpha 1 (Gq)
granule cells = beta 1 (Gs)
What is the third stimulus to renin release?
- with a fall in the blood volume, the venous pressure falls, as the venous system is the main source of capacitance in the circulation
- this fall causes a fall in h pressure in the vasa recta, and hence an increase in the uptake of fluid from the renal interstitital space
- this means a greater loss of fluid from the filtrate, paticululary in the descending limb of LoH
- this decrease Na+ delivery to the distal tubule acts as a further stimulus to renin
What causes ADH release after haemorrhage?
How can this cause hyponatraemia?
Deceased cardiac filling, activation of baroreceptor reflex, and the central actions of ATII all increase the release of ADH
THis release leads to an increase in water reabsorption and hence the maintainence of circulating volume
THis effect will lower osmolality because this mechanism does not retain Na+
Describe the interaction between osmoregulation and volume regulation
volume regulation disturbs osmoregulation
The body accepts decreased osmolality in order to maintain low volume
What 4 things cause the relase of ADH?
What 3 things causes the inhibition of ADH release?
Release - increased osmolality - stress - decreased volume - nicotine Inhibition of release - alcohol - increased volume - decreased osmolality
