Volume regulation

Question 1

What does effective circulating volume change together with?

Answer 1

Extracellular volume

Question 2

What shift of fluid occurs during heart failure?

Answer 2

The change in pressure and volume of circulating blood causes fluid to shift from ECF to circulating fluid and therefore requires retention of water.

Question 3

What is the juxtaglomerular apparatus?

Answer 3

A complex in the late distal tubule and its association with the afferent arteriole, in order to regulate BP and GFR.

Question 4

What components make up the juxtaglomerular apparatus?

Answer 4

Macula densa cells in the DT

Juxtaglomerular cells within the afferent arterioles

Question 5

What do macula densa cells detect? What effect do they produce?

Answer 5

Detect elevated Na levels being moved by NKCC2 as more water absorption being required. The cells release ATP to produce adenosine causing vasoconstriction of the afferent arteriole to reduce GFR

Question 6

What do juxtaglomerular cells detect and what effect do they produce?

Answer 6

As BP falls they secrete RENIN (under sympathetic control) for the production of ANGII causing:

• vasoCONSTRICTION
• increased Na reabsorption in PT for water retention
• ALDOSTERONE release for increased Na reabsorption in DT and MCD. (Impacts macula densa)

Question 7

Other than low BP triggering release of RENIN, what else can trigger aldosterone?

Answer 7

Hyperkalaemia

Question 8

What medical treatment is used to control BP / Used as ANTIHYPERTENSIVES?

Answer 8

INHIBIT RAAS:

• ACEi (pril)
• ARBs (sartan) = AngII receptor antagonist
• Aldosterone receptor anatagonist e.g. spironolactone
• Renin inhibition e.g. Aliskiren
• Beta blockers (stops renin release)

Question 9

What are the side effects of ACEi?

Answer 9

Causes a cough as bradykinin and substance P are not broken down leading to bronchodilation

Question 10

Where does AngII act and what is its effect?

Answer 10

AT1 receptors in the periphery. AT1 is a GqPCR causing increased IP3/DAG signalling for increased Ca release from smooth muscle and JG cells to:
-Vasoconstrict
-Increase Na/H exchanger in PT
-Increased Aldosterone release
-ADH release and thirst
=Increased circulating volume to increase BP

Question 11

What levels fall during a haemorrhage?

Answer 11

BP, CO, Venous and arterial volume

Question 12

What does a fall in BP trigger?

Answer 12

Increased sympathetic activity for RENIN release from granules in the afferent arterioles = vasoconstriction

Question 13

How does sympathetic innervation cause vasodilation?

Answer 13

Sympathetic activity acts via alpha1 receptors for vasoconstriction to create an even further fall in BP so that Renin release is enhanced.
Directly stimulates renin release via beta1 receptors.

Question 14

What NT does sympathetic innervation use and what type of receptors does it act at?

Answer 14

NAd
Alpha1 is a Gq coupled adrenoreceptor
Beta1 is a Gs coupled adrenoreceptor on the granule cells

Question 15

How does a fall in blood pressure cause increased Na movement via NKCC?

Answer 15

As blood volume falls, vasa recta pressure falls so there is increased reabsorption of water from the intersitium. More reabsorption from filtrate means more Na reabsorption from DT via NKCC, stimulating renin release from JGA.

Question 16

What does reduced cardiac filling activate?

Answer 16

BARORECEPTOR REFLEX and AngII and ADH release.

Question 17

How does volume regulation disrturb osmoregulation?

Answer 17

As more water is reabsorbed due to ADH, it creates a low osmolality as Na is not retained when using ADH = hyponatraemia.

Question 18

What is the primary affect of ADH?

Answer 18

To reduce osmolality

Question 19

What factors cause ADH release and which inhibit?

Answer 19

\+ Increased osmolality
\+Decreased volume
\+Nicotine
\+Stress
-Decreased osmolality
-Increased volume
-Alcohol

Question 20

What is ANP and why is it released?

Answer 20

Atrial natriuretic peptide. It is released upon atrial filling when there is an increased VR.

Question 21

What is the effect of ANP?

Answer 21

ANP travels to ANPa,b receptors in the kidney to activate cGMP:
-Inhibit Na/K ATPase to DILATE afferent arterioles and increase GFR and Na delivery to INHIBIT RAAS
-Reduce Na/Cl cotransport in DT
-Reduce ENAC activity in MCD
= Increases Na excretion to lose circulating volume

Question 22

What peptide works in a similar way to ANP?

Answer 22

Urodiliation - a peptide in the kidney

Question 23

Why are PGs produced?

Answer 23

Produced tonically to increase Na excretion and reduce plasma volume. e.g. PGE2 and PGI2

Question 24

What will inhibit PG pathway?

Answer 24

NSAIDS inhibits tonic PG release by blocking COX pathway for Na RETENTION

Question 25

What are the affects of NSAIDs in a Pt with renal failure?

Answer 25

Have the opposite effects = Na EXCRETION

Question 26

What effect does dopamine have on the renal system and where is it produced?

Answer 26

Synthesised in PT sympathetic nerve terminals to act tonically at D1 receptors. It increases cAMP and reduces Na/H exchanger for Na EXCRETION and therefore reduced plasma volume.