ECF Volume Regulation 1

Question 1

What is the distribution of total body water between cels are ECF determined by?

Answer 1

The number of osmotically active particle in each compartment

Question 2

Name the important osmotically active particles in each compartment

Answer 2

• Na+ and Cl- are the major ECF osmoles.
• K+ salts are the major ICF osmoles.
• Regulation of ECF volume -> Regulation of body Na+ (retain more Na, more water moves in)

Question 3

How does Na effect distribution of water?

Answer 3

Changes in Na+ content of the ECF will -> changes in ECF volume and therefore will affect the volume of blood perfusing the tissues = effective circulating volume and therefore BP

I.e. Increase Na -> increase water content of body -> increase plasma volume -> increase BP

Question 4

What is he regulation of Na dependent on?

Answer 4

High and low pressure baroreceptors

Question 5

What are the steps in Na effecting high and low presser barorectors?

Answer 5

↑ salt and H2O loss as in vomiting, diarrhoea or excess sweating -> ↓ plasma volume -> ↓ venous pressure -> ↓ VR -> ↓ atrial P (less distortion indicating less ‘fullness’) -> ↓ EDV -> ↓ stroke volume -> ↓ CO -> ↓ BP -> ↓ carotid sinus baroreceptor inhibition of sympathetic discharge to cause vasoconstriction to increase BP

-> ↑ sympathetic discharge -> ↑ vasoconstriction -> ↑ TPR -> ↑ BP towards normal

Question 6

What stimulated the ADH secretion in loss of decreased plasma?

Answer 6

Decrease firing of low and high pressure baroreceptors

Question 7

What is the effect of vasoconstriction in the sympathetic nervous system response to decreased plasma volume?

Answer 7

Vasoconstriction in the renal arteries -> ↑ renin release

Question 8

What is the function of renin?

Answer 8

Regulates water and Na reabsorption by the kidney -> release of angiotensin II -> increase reabsorption directly on prox. Tubule and indirectly of distal tubule.

Question 9

What is the effect of increased sympathetic discharge (due to low plasma volume) on the kidney?

Answer 9

↑renal VC nerve activity -> ↑ renal arteriolar constriction and an ↑ in renin

Question 10

What is the effect of increased renin in response to increased sympathetic discharge?

Answer 10

↑ renin -> ↑ angiotensin II -> ↓ peritubular capillary hydrostatic P (+ the oncotic p) -> ↑ Na+ reabsorption from the proximal tubule and therefore less Na+ excreted and more water reabsorbed.

-> ↑ renin -> ↑ angiotensin II -> ↑ aldosterone -> ↑ distal tubule Na+ reabsorption and therefore less Na+ excreted.

Question 11

What allows an ↑ Na reabsorption from proximal tubule in response to increase sympathetic discharge?

Answer 11

Greater reabsorptive forces in peritubular capillaries (↑ oncotic and ↓ hydrostatic p)

Question 12

What is the reabsorptive range of Na in the proximal tubule?

Answer 12

65% in volume excess to 75% in volume deficit (range due to changes in starling’s forces)

Question 13

How does the GFR remain unchanged?

Answer 13

Autoregulation maintains GFR and the vasoconstriction of afferent and efferent means little effect on GFR until volume depletion severe enough to cause considerable ↓ MBP

Question 14

What is the physiological response of the kidney to hypovolemia?

Answer 14

PPC < normal therefore efferent arteriole constriction by angiotensin II and oncotic p > normal therefore loss NaCl and H2O so [plasma protein] ↑ -> drives NaCl and H2O into capillaries

There is constriction of afferent arteriole, but coupled angiotensin II mediated efferent constriction maintains GFR

Question 15

What is the physiological response of the kidney to hypervolemia?

Answer 15

PPC > normal therefore efferent arteriole is less constricted and oncotic p < normal therefore plasma proteins are diluted by retention of salt and water

Question 16

What is Na reabsorption from the distal tubule controlled by?

Answer 16

Aldosterone

Question 17

What is the specialisation of afferent arterioles to maintain Na content?

Answer 17

Smooth muscle of the media of afferent arterioles contains large epithelial cells; Juxtaglomerular cells (JG) which monitor pressure and Na content

Question 18

What two structures form the juxtaglomerular apparatus?

Answer 18

Juxtaglomerular cells and the macula dense (specialised loop of distal tubule)

Question 19

How is the juxtaglomerular apparatus structured?

Answer 19

The ascending loop, becoming the distal tubule, loops back around and is in close relation the JG cells of the arterioles -> macula densa cells which can detect blood pressure and Na content.

Question 20

How is renin activated?

Answer 20

Low BP detected by the juxtaglomerular apparatus

Question 21

What produces renin?

Answer 21

JG cells

Question 22

What is renin?

Answer 22

A proteolytic enzyme which acts on a large protein in the alpha2-globulin fraction of the plasma proteins = angiotensinogen

Question 23

What is the function of renin?

Answer 23

Converts Angiontensinogen -> angiontensin I (and ACE converts angiotensin I -> angiotensin II)

Rate limiting step is concentration of renin; more renin, more angiontensin II produced

Question 24

What is the function of angiotensin II?

Answer 24

Causes vasoconstriction and stimulation of aldosterone and thirst to increase blood volume, which then has a positive effect on the rest of the angiontensin II actions.

Question 25

List the effects of angiotensin II

Answer 25

• Arterioles -> vasoconstriction
• Kidneys -> Na reabsorption
• Sympathetic NS -> increase release of noradrenaline
• Adrenal cortex -> release of aldosterone
• Hypothalamus -> increases thirst and ADH release

Question 26

What controls the release of renin?

Answer 26

• Pressure in afferent arterioles decrease (detected by JG cells)
• ↑ Sympathetic NS (via beta-1 effect)
• Inversely proportional to rate of delivery of NaCl at macula dense (specialised distal tubule)
• Angio. II neg feedback to inhibit renin
• ADH inhibits renin release

Question 27

Wh tis angiotensin II important in the body’s repose to hypovolemia?

Answer 27

1. It stimulates aldosterone and therefore NaCl and H2O retention in the blood.
2. It is a very potent biological vasoconstrictor, 4-8 x more potent than noradrenalin, therefore contributes to ↑ TPR
3. It acts on the hypothalamus to stimulate ADH secretion -> ↑ H2O reabsorption from CD.
4. It stimulates the thirst mechanism and the salt appetite (in the hypothalamus).

Question 28

What is the tubuloglomerular feedback?

Answer 28

Mechanism used to regulate GFR

Question 29

How does the tubuloglomeular feedback system work?

Answer 29

Increase in GFR -> more flow in the tubule -> ↑ Na delivery to macular densa -> constrict afferent arterioles -> decrease flow to Bowman’s capsule -> filtration decreased -> hydrostatic pressure in glomerulus decreases -> GFR decreases

Question 30

What would be the effect of a Pt who has lost 3L of salt and water (from ECF) and drinks 2L of pure water, and what is the outcome?

Answer 30

There will be opposing inputs to ADH secreting cells:
↓ ECF osmolarity -> inhibition of ADH via osmoreceptors (because water would diffuse out of solution and decrease osmolarity further)

↓ ECF volume -> ↑ ADH via baroreceptors

Volume considerations have primacy is effective circulating volume is compromised, so ADH ↑ because of the bare receptors, even though this is associated with hypoosmolarity

Question 31

What is more important in emergency situation (wrt ADH release) if osmolarity is decreased in ECF, but insufficient volume?

Answer 31

Normally osmolarity is main determinant of [ADH], but if sufficient volume change occurs which can compromised brain perfusion, ECF volume become primary drive for [ADH].

Once volume is restored in hypovolaemia, then osmolarity will be normalised and again becomes main determinant of ADH.

Question 32

What is the main determinant of [ADH]?

Answer 32

Osmolarity of ECF