the body uses Na+ regulation to regulate Total Body Water (TBW). What receptors are involved in detecting changes in TBW?
Low perssure baroreceptors in atria & Great veins
High pressure baroreceptors in the Carotid sinus and aortic arch
How do baroreceptors respond to Hypovolaemia?
Atrial and carotid receptors decrease ADH inhibition (normally osmoreceptors control ADH, but at sufficiently low plasma volumes to disrupt brain perfusion volume receptors take over)
Carotid receptors also trigger sympathetic Tone –> Vasoconstriction and renin release
What are the effects of sympathetic tone on the blood pressure?
1) Vasoconstriction -> TPR increase -> BP increase
2) Direct stimulation of Renin release via B1 receptors
3) Renal arteriole constriction (Maintains GFR)
So carotid baroreceptors detect a low plasma volume –> Trigger Symp nerves –> renin release, what else triggers renin release in a patient who’s dehydrated (due to say diarrhoea, vomiting or sweating)?
The low plasma volume and consequent low NaCl in the kidney itself:
- Plasma volume detected by Juxtaglomerular cells
- Low NaCl detected by Macula Densa Cells
What are the Juxtaglomerular cells and Macula Densa?
JG are large granular epithelial cells in the tunica media of the afferent arteriole. they detect a reduction in distension when plasma volume drops.
Macula densa is a group of specialised cells of the ascending loop of henle (where it passes the glomerulus) that detect NaCl
Together they are the Juxtaglomerular Apparatus
What does renin do?
Its a proteolytic enzyme that cleaves circulating Angiotensinogen into Angiotensin I
Where is angiotensinogen made?
In the liver, fairly continuously
What happens to angiotensin I?
Its converted to Angiotensin II by ACE, which is found in the endothelium of most vessels, particularly in the pulmonary circuit
Which step in angiotensin II production is the rate limiting step?
Renin release because;
- Angiotensinogen is continuously released
- ACE is always present in most of the endothelium
5 things alter renin release, ?
1) JG cells detecting plasma volume (“Renal Baroreceptors”)
2) Macula Densa cells detecting less delivery of NaCl round the Asc Loop of henle
3) Direct Sympathetic stimulation on B1 receptors
4) Inhibited by ADH (part of osmolarity control)
5) Angiotensin II has a -ve feedback effect
What does Angiotensin II?
Ultimately raises blood volume while maintaining osmolarity leading to a rise in BP:
1) Vasoconstriction to raise TPR
2) Increases CV response via medulla oblongata
3) Increases ADH & Thirst from Hypothalamus
4) Stimulates Aldosterone release from Zona Glomerulosa –> Na+ reabsorption in distal tubule
5) Raises Na+ reabsorption in proximal tubule
How does angiotensin II raise Na reabsorption in the Proximal Tubule?
It vasoconstricts the efferent arteriole creating a low hydrostatic pressure in the downstream peritubular capillary tubule
coupled with the fact that low plasma volume –> high plasma protein –> High capillary oncotic pressure
Means water and Na reabsorped
How is GFR autoregulated through hypovolaemia?
Symp Discharge –> Constricts Afferent Arteriole
Angiotensin II –> constricts Efferent Arteriole
What is more important to the body. ECF osmolarity or ECF volume?
ECF osmolarity when the volume is within normal range.
But when volume gets low enough to risk affecting brain perfusion (hypovolaemia) it takes over as the primary driver.
So if you lose salt and water to diarrhoea then drink some water your still hypovolaemic and also now hypoosmolar.
Baroreceptors will still increase ADH to bring your volume back to normal even though it will worsen the hypoosmolarity.
What happens when the body actually has excess Sodium?
you retain water leading to hypervolaemia
-> Detected by Atrial baroreceptors
-> Atrial Natriuretic Peptide released (ANP)
-> Promotes Na+ excretion (& so water)
Known as the “aldosterone escape”
How does ANP increase Na+ Excretion?
1) decreases ADH release
2) Increases GFR
3) Decreases Renin release
4) Decreases Aldosterone release directly
Also lowers CV response in medulla oblongata to decrease BP
In what situation would you have excess sodium?
A tumour of adrenal cortex secreting excess Aldosterone –> Na+ retention & K+ loss
Because of the aldosterone escape (ANP) these patients arn’t actually very hypernatraemic, but are still Hypokalemic
What is osmotic diuresis?
A process by which lose the concentration gradient produced by your loop of henle and piss lots of isotonic urine due to a solute getting stuck in the tubule
What is the major cause of osmotic diuresis?
Excess Glc in Uncontrolled DM.
Glc exceeds its Tm and the excess remains in the proximal tubule instead of being reabsorped (causing water retention in tubule)
Still talking about osmotic diuresis, excess glc causes water retention, what other consequence does this have in the proximal tubule?
The excess H2O being retained dilutes the tubule.
Na+ can longer be reabsorped passively down it’s conc gradient and so -> Excess sodium retained in tubule
What effect does the Na+ retention in the proximal tubule during osmotic diuresis have on the proximal tubule?
further decreases Glc Reabsorption making the whole thing worse
Because Na is needed for glucose reabsorption (SGLT symporter)
During osmotic diuresis excess Glc, water & Na have been retained in the proximal tubule, what happens when they reach the loop of henle?
First the extra solutes means water doesn’t move out in the desc. limb so the fluid entering the asc. limb isn’t concentrated
Second the less concentrated fluid in asc. limb means NaCl pumps don’t have a gradient down which to move NaCl out the tubule
Causes high solute/H2O volume fluid to reach the distal tubule and gradually abolishes the medullary interstitial gradient