Regulation of ECF Volume I

Question 1

what are the major ecf osmoles?

Answer 1

Na+ and Cl-

Question 2

what are the major ICF osmoles?

Answer 2

K+ salts

Question 3

Regulation of ECF volume ≡

Answer 3

Regulation of body Na+

Question 4

describe the distribution of body water?

Answer 4

Question 5

what will changes in the content of Na+ cause?

Answer 5

changes in ECF volume and ∴ will affect the volume of blood perfusing the tissues = effective circulating volume and ∴BP.

Question 6

what is regulation of Na+ dependent on?

Answer 6

high and low P baroreceptors.

Question 7

what is the renal response to a decreased ECF volume?

Answer 7

(hypovolaemia)

↑salt and H2O loss as in vomiting, diarrhoea or excess sweating → ↓ PV→ ↓ venous P → ↓ VR → ↓ atrial P → ↓ EDV →↓ SV →↓ CO→↓ BP →↓ carotid sinus baroreceptor inhibition of sympathetic discharge.

→↑ Sympathetic discharge →↑VC →↑ TPR →↑ BP towards normal.

Question 8

effect of increased sympathetic discharge on the kidney?

Answer 8

↑ renal VC nerve activity →↑ renal arteriolar constriction and an ↑in renin

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

renin →↑ angiotensin II→ ↑ aldosterone →↑ distal tubule Na+ reabsorption and ∴ less Na+ excreted.

Changes in proximal tubule Na+ reabsorption are due to changes in the rate of uptake by the peritubular capillaries.
Determined by Πp

Question 9

Na+ reabsorption?

Answer 9

↑in Na+ reabsorption is because of greater reabsorptive forces in the peritubular capillaries.

If have lost NaCl and H2O, ∴more of the “wet stuff”, then Πp↑ even more than normal (ie > than that due to loss of filtration fraction) so can reabsorb up to 75% of the filtrate at the proximal tubule.

(So reabsorptive range in proximal tubule; 65% in volume excess to 75% in volume deficit. Big range of volume just because of changes in Starling’s forces.)

Question 10

what maintains GFR and VC?

Answer 10

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

Question 11

what is the regulation of distal tubule Na+ reabsorption is under the control of?

Answer 11

adrenal cortical steroid hormone, aldosterone.
Very important in the long-term regulation of Na+ and ECF volume.

Question 12

what are juxtaglomerular cells?

Answer 12

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

Question 13

what is the macula densa?

Answer 13

They are closely associated with a histologically specialized loop of the distal tubule
The two together form the Juxtaglomerular apparatus.

Question 14

what is aldosterone secretion controlled by?

Answer 14

Aldosterone secretion controlled by reflexes involving the kidneys themselves.

Question 15

what do JG cells produce?

Answer 15

the hormone renin, a proteolytic enzyme which acts on a large protein in the α2-globulin fraction of the plasma proteins = angiotensinogen.

JG cells act as “renal baroreceptors”, less distension → ↑ secretion of renin. Intrinsic property, occurs if denervated.

Question 16

what does renin do?

Answer 16

off the decapeptide angiotensin I which is then converted by enzymes in the endothelium to the active octapeptide = angiotensin II

Question 17

what is ACE, where is it found?

Answer 17

angiotensin converting enzyme

It is found throughout the vascular endothelium, but the greatest proportion of the conversion occurs as the blood passes through the pulmonary circuit, but all of the endothelium is important.

Question 18

describe the role of angiotensin 2?

Answer 18

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.

The rate limiting-step is the release of renin since angiotensinogen is always present in plasma.

Question 19

what is the rate limiting step in conversion of angiotensin?

Answer 19

The rate limiting-step is the release of renin since angiotensinogen is always present in plasma.

Question 20

what controls renin release?

Answer 20

↑ Renin release when P in afferent arteriole at the level of the JG cells ↓.↑

Sympathetic nerve activity causes ↑ renin release via β1 effect

Rate of renin secretion is inversely proportional to rate of delivery of NaCl at the macula densa (specialized distal tubule)
↓ NaCl delivery → ↑ renin

Angiotensin II feeds back to inhibit renin.

ADH inhibits renin release (osmolarity control).

Question 21

what is the relationship like between afferent arterioles and JG cells?

Answer 21

Close relationship between afferent arteriole with JG cells and macula densa provides mechanism for controlling input and output of tubules and basis of tubuloglomerular balance.

Question 22

describe the action of angiotensin 2 in hypovolaemia?

Answer 22

1.It stimulates aldosterone and ∴ NaCl and H2O retention.

2. It is a very potent biological vasoconstrictor, 4-8 x more potent than NE, ∴ 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 23

what occurs in hypovolaemia?

Answer 23

↑ proximal AND distal tubule Na+ reabsorption together with osmotic equivalents of H2O, helps restore volume deficits, mediated by CV reflexes.

Question 24

what contributes to GFR constancy?

Answer 24

Question 25

Consider a person suffering from severe diarrhoea, who has lost 3l of salt and water (from ECF) and drinks 2 l of pure water:
There will be opposing inputs to ADH secreting cells:

ECF osmolarity → inhibition of ADH via osmoreceptors

↓ ECF volume → ↑ADH via baroreceptors

what would happen in this situation?

Answer 25

V.I.F. Volume considerations have primacy if ECV is compromised, so that ADH will ↑because of the baroreceptors, even though this is associated with hypoosmolarity.

Question 26

when is volume consideration more important than osmolarity?

Answer 26

Normally, osmolarity is the main determinant of [ADH], but if sufficient volume change to compromise brain perfusion, then volume becomes the primary drive, so to conserve volume, tolerate disturbed osmolarity.
Once volume is restored in hypovolaemia, then osmolarity will be normalized and again becomes main determinant of ADH.

Question 27

lose water ______?

Answer 27

infuse or drink saline - lose water, replace salt and water

Question 28

what does aldosterone promote?

Answer 28

Na+ reabsorption

Question 29

what does ANP promote?

Answer 29

Na+ excretion

Question 30

what happens if aldosterone is given to normal subjects?

Answer 30

If Aldosterone is given to normal subjects on an adequate Na+ diet, there will be Na+ retention and K+ loss.

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 31

what happens in patients with conns syndrome?

Answer 31

hyperaldosteronism, due to a tumour of the adrenal cortex, they are K+ depleted, but not hypernatraemic.

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

Actions may be to inhibit secretion of renin, generally oppose the actions of angiotensin II.

Question 32

why is osmotic diuresis important to consider in terms of hypovolaemia?

Answer 32

Illustrates how renal function can be disrupted and is most important clinically in explaining the effects of uncontrolled diabetes mellitus in producing hyperglycaemic coma.

In uncontrolled DM, where [BG] is not kept within strict control, the high plasma glucose level exceeds the maximum reabsorptive capacity in the proximal tubule

Question 33

describe osmotic diuresus in an uncontrolled diabetic?

Answer 33

1. Glucose remains in the tubule and exerts an osmotic effect to retain H2O in the tubule
2. ∴ [Na+] in the lumen is decreased because the Na+ is present in a larger volume.

Since Na+ gains access to the proximal tubule cells by passive diffusion down a concentration gradient created by the active transport out of the basolateral surfaces, Na+ reabsorption will be ↓

→ ↓ ability to reabsorb glucose since it shares a symport with Na+.

3. In the descending limb of the loop of Henle, movement of H2O out of the tubule into the interstitium is reduced because the glucose and excess Na+ exert an osmotic effect to retain H2O.
   ∴ fluid in the descending limb is not so concentrated.
4. This means that the fluid delivered to the ascending limb is less concentrated.
   Since the NaCl pumps in ascending limb are gradient limited, medullary interstitial gradient is much less.
   ∴ there is a considerable reduction in the volume of NaCl and H2O reabsorbed from the loops of Henle,
   so a large volume of NaCl and H2O is delivered to the distal tubule.
   AND the interstitial gradient is gradually abolished.
5. Under normal conditions, a large volume of NaCl and H2O delivered to the distal tubule means there is excess ECF volume and ∴ need to get rid of NaCl and H2O.
   The macula densa will detect the high rate of delivery of NaCl so that renin secretion will be suppressed and
   ∴ Na+ reabsorption at the distal tubule will be decreased.

Question 34

summarise the effects on uncontrolled diabetes on rebasorbtion of h20?

Answer 34

Question 35

A large volume of nearly isotonic urine will be excreted → ↓ PV.

Answer 35

The ↓ PV will stimulate ADH release via baroreceptors but cannot be effective because the interstitial gradient has run down.
Patients with uncontrolled DM can produce urine volumes of up to 6-8 l/day, causing severe salt and water depletion.
If ingestion is not adequate, a raging thirst is one of the first signs of DM, then the hypotension may be so severe as to cause a hyperglycaemic coma.
This is due to inadequate BF to the brain whereas a hypoglycaemic coma is due to inadequate glucose for the brain.