ECF volume regulation

Question 1

What % of total body water is found in the ECF?

Answer 1

1/3 so around 14L

Question 2

What volume is total body water?

Answer 2

42L

Question 3

What % of total body water is found in the ICF?

Answer 3

2/3 so around 28L

Question 4

What makes up ECF?

Answer 4

Plasma + Interstitial fluid

Question 5

What determines body fluid distribution?

Answer 5

Since H2O can freely cross all cell membranes, the body fluids are in osmotic equilibrium, so that the distribution of total body water (TBW) between cells and ECF is determined by the number of osmotically active particles in each compartment.

Question 6

How do the kidneys respond to a decrease in ECF volume (hypovolaemia)?

Answer 6

o ↑Salt and H2O loss as in vomiting, diarrhoea or excess sweating → ↓ PV→ ↓ venous P → ↓ vascular resistance (VR) → ↓ atrial pressure → ↓ end diastolic volume →↓ stroke volume →↓ cardiac output →↓ BP →↓ carotid sinus baroreceptor inhibition of sympathetic discharge.

o →↑ Sympathetic discharge →↑ vasoconstriction (VC) →↑ total peripheral resistance →↑ BP towards normal

Question 7

What can cause hypovolaemia?

Answer 7

Vomiting, diarrhoea and sweating profusely

Question 8

How does sympathetic activity change Na levels?

Answer 8

↑ Sympathetic discharge causes:

o ↑ Renal vasoconstrictive nerve activity →↑ renal arteriolar constriction and an ↑in renin

o ↑Renin →↑ angiotensin II→ ↓ peritubular capillary hydrostatic pressure (+ the ↑Πp) →↑ Na+ reabsorption from the proximal tubule and ∴less Na+ excreted.

• ↑Renin →↑ angiotensin II→ ↑ aldosterone →↑ distal tubule Na+ reabsorption causing less Na+ to be excreted.
• Changes in proximal tubule Na+ reabsorption are due to changes in the rate of uptake by the peritubular capillaries.

Question 9

How is GFR maintained during hypovolaemia?

Answer 9

Due to the constriction of afferent due to sympathetic VC coupled with Angiotensin II mediated constriction of efferent maintains GFR

Question 10

What hormone regulates distal tubule Na+ reabsorption, and therefore also ECF regulation?

Answer 10

Aldosterone

Question 11

Describe the Juxtaglomerular apparatus

Answer 11

• Smooth muscle of the media of the afferent arteriole, just before it enters the glomerulus has become specialized, containing large epithelial cells with plentiful granules = Juxtaglomerular cells (JG).
• They are closely associated with a histologically specialized loop of the distal tubule = the macula densa. The two together form the Juxtaglomerular apparatus.

Question 12

What is the role of Juxtaglomerular cells in ECF regulation?

Answer 12

• JG cells produce the hormone renin, a proteolytic enzyme which acts on a large protein in the α2-globulin fraction of the plasma proteins angiotensinogen.
• Renin splits off the decapeptide angiotensin I which is then converted by ACE in the endothelium to the active octapeptide = angiotensin II
• Angiotensin II stimulates the aldosterone- secreting cells in the zona glomerulosa of the adrenal cortex.
• The aldosterone passes in the blood to the kidney where it stimulates distal tubular Na+ ion reabsorption.

Question 13

What controls renin release?

Answer 13

1. ↑ Renin release when the pressure in the afferent arteriole at the level of the JG cells ↓
2. ↑ Sympathetic nerve activity causes ↑ renin release via β1 effect
3. Rate of renin secretion is inversely proportional to rate of delivery of NaCl at the macula densa (specialized distal tubule) - ↓ NaCl delivery → ↑ renin
4. Angiotensin II feeds back to inhibit renin
5. ADH inhibits renin release (osmolarity control)

Question 14

What stimulates renin release?

Answer 14

Decreased pressure detected by JG cells
Increased sympathetic activity
Decreased NaCl delivery to the distal tubule

Question 15

What inhibits renin release?

Answer 15

Angiotensin II

ADH

Question 16

How is angiotensin II so fundamentally important in the body’s response to hypovolaemia?

Answer 16

o It stimulates aldosterone and ∴ NaCl and H2O retention.

o It is a very potent biological vasoconstrictor, 4-8 x more potent than norepinephrine, ∴ contributes to ↑ total peripheral resistance (TPR)

o It acts on the hypothalamus to stimulate ADH secretion → ↑ H2O reabsorption from CD.

o It stimulates the thirst mechanism and the salt appetite (in the hypothalamus).

Question 17

How should you treat large losses of water and salts?

Answer 17

Infuse or drink saline, not pure water!

Question 18

What hormone promotes Na reabsorption?

Answer 18

Aldosterone promotes Na+ reabsorption

Question 19

What hormone promotes Na excretion?

Answer 19

ANP (Atrial Natriuretic Peptide) promotes Na+ excretion.

Question 20

What would happen if aldosterone was given to a person on a adequate Na diet?

Answer 20

• If Aldosterone is given to normal subjects on an adequate Na+ diet, there will be Na+ retention and K+ loss both from the distal tubule
• There will be a weight gain of 2-3kg due to the Na+ and H2O retention.
• After a couple of days, a spontaneous diuresis occurs 2° to volume expansion, although K+ loss persists.

Question 21

What would you expect biochemically on plasma analysis of someone with Conns syndrome?

Answer 21

Patients with Conn’s syndrome, or 1° hyperaldosteronism, due to a tumour of the adrenal cortex, are K+ depleted, but not hypernatraemic.

Question 22

When is ANP secreted?

Answer 22

ANP is secreted by atrial cells in response to expansion of ECF volume and causes natriuresis, loss of Na+ and H2O in urine.