Volume Regulation Flashcards
Define effective circulating volume.
What is the clinical usefulness of measuring it?
- The volume of arterial blood that is effectively perfusing tissues.
- It is used as an indicator for total extracellular water content.
What is the juxtaglomerular apparatus?
The complex of the distal tubule in association with the renal afferent arteriole of the same nephron.
What cells are contained within the afferent arteriole at the juxtaglomerular apparatus?
Granular (juxtaglomerular) cells.
What is the macula densa?
A thickening of the wall of the distal tubule.
What is the function of the cells of the macula densa?
To detect Na+ concentration.
Describe the stages of the renin-angiotensin system.
1 - The macula densa detects low Na+ concentration in the distal tubule.
2 - The granular (juxtaglomerular) cells at the afferent arteriole are stimulated to produce renin.
3 - Renin converts angiotensinogen (from the liver and adipocytes) into angiotensin 1.
4 - Angiotensin converting enzyme (ACE) in the lungs converts angiotensin 1 into angiotensin 2.
5 - Angiotensin 2 causes efferent vasoconstriction, increasing GFR (first negative feedback mechanism).
6 - Angiotensin 2 increases Na+ reabsorption in the proximal tubule, increasing body Na+ and volume (second negative feedback mechanism by increasing GFR).
7 - Angiotensin 2 stimulates aldosterone release from the adrenal cortex.
8 - Aldosterone increases Na+ reabsorption at the distal tubule and the collecting duct, increasing body Na+ and volume (third negative feedback mechanism by increasing GFR).
List 2 triggers for aldosterone release.
1 - Angiotensin 2.
2 - Hyperkalaemia.
Why is it important that aldosterone is not the only mechanism by which angiotensin 2 regulates body volume?
- If aldosterone was the only mechanism for angiotensin 2, then K+ could not be regulated independently of volume regulation, because changes in K+ would have to also lead to changes in body volume (since K+ and angiotensin 2 both use aldosterone to mediate their regulation).
- Since there are other mechanisms of angiotensin 2, volume regulation can be regulated independently of K+.
List 4 drug classes that inhibit the renin-angiotensin system.
1 - ACE inhibitors.
2 - Angiotensin 2 type 1 receptor (AT1) antagonists.
3 - Aldosterone receptor antagonists.
4 - Renin inhibitors.
List 6 locations in the body where angiotensin 2 type 1 (AT1) receptors might be found.
1 - Heart.
2 - Lungs.
3 - Vessels.
4 - Kidney.
5 - Adrenal cortex.
6 - Brain.
List 2 ACE inhibitors.
1 - Captopril.
2 - Enalapril.
List 2 angiotensin 2 type 1 (AT1) receptor antagonists.
1 - Candesartan.
2 - Irbesartan.
Give an example of an aldosterone receptor antagonist.
Spironolactone.
Give an example of a renin inhibitor.
Aliskiren.
Through which pathway do angiotensin 2 type 1 receptors mediate their effects?
The Gq pathway.
Give an example of a side effect of ACE inhibitors.
Coughing.
List 2 other ways by which angiotensin 2 increases circulating volume (other than those stated in the RAS card).
1 - Causes ADH release.
2 - Causes thirst.
List 3 cardiovascular effects of haemorrhage.
1 - Decreased vascular volume (and pressure).
2 - Decreased cardiac filling (and output).
3 - Decreased tissue and organ perfusion.
List the ways by which the renin-angiotensin system is triggered.
1 - Sympathetic nerves stimulate granular cells directly to secrete renin.
2 - Sympathetic nerves cause afferent vasoconstriction to further decrease perfusion pressure, which is sensed by the granular cells directly.
3 - Afferent vasoconstriction lowers GFR, so decreases distal Na+ and decreases wall tension, which is sensed by the macula densa.
4 - A fall in blood pressure causes a fall in pressure in the vasa recta, which increases fluid uptake from the renal interstitial space. This means that Na+ concentration will be lower at the distal tubule, which is sensed by the macula densa.
Which sympathetic receptors are present on:
- The smooth muscle of the vessels supplying the kidney?
- The granular cells?
- The smooth muscle of the vessels supplying the kidney have alpha 1 adrenoceptors.
- The granule cells have beta 1 adrenoceptors.
Via which pathway do alpha 1 and beta 2 adrenoceptors mediate their effects?
- Alpha 1 receptors use the Gq pathway.
- Beta 2 receptors use the Gs pathway.
List 3 ways by which ADH release is increased following sudden volume loss.
1 - Decreased cardiac filling.
2 - Activation of the baroreceptor reflex.
3 - The central actions of angiotensin 2.
Why does the acute response to haemorrhage involve hyponatraemia?
Because ADH release is increased following haemorrhage, which retains water but does not retain Na+.
List 3 negative stimuli and 3 positive stimuli for ADH release.
Positive stimuli:
1 - Increased osmolality.
2 - Decreased volume.
3 - Nicotine.
Negative stimuli:
4 - Decreased osmolality.
5 - Increased volume.
6 - Alcohol.
What is the primary effect of ADH?
To drop osmolality (rather than increase volume, which is its secondary effect).
List 3 functions of atrial natriuretic peptide (ANP).
Has natriuretic functions:
1 - Increases cGMP activity in the kidney, resulting in dilation of the afferent glomerular arteriole, increasing GFR.
2 - Decreases Na+ / Cl- cotransport activity in the distal tubule.
3 - Decreases ENaC and Na+ / K+ ATPase activity in the cortical collecting duct.
What stimulates atrial natriuretic peptide release?
Where is it produced?
- Increased atrial filling.
- It is produced by cardiac myocytes of the atria.
To which receptors does atrial natriuretic peptide (ANP) bind?
ANPa and ANPb receptors (in the kidney).
Give an example of a peptide that is similar to atrial natriuretic peptide (ANP) in function but is produced in the kidney.
Urodilatin.
What effect do prostaglandins have on renal function?
They have a natriuretic function.
Where in the kidney is dopamine produced?
In sympathetic nerve terminals in the proximal tubule.
What effect does dopamine have on renal function?
It has a natriuretic function.
To which receptors does dopamine bind to mediate its effects on renal function?
D1 and D2 receptors.
How does dopamine mediate its effect on renal function?
1 - By inhibiting the Na+ / H+ exchanger in the proximal tubule (luminal / apical membrane).
2 - By inhibiting the Na+ / K+ ATPase activity (basolateral membrane).
