Regulation of ECF Volume I Flashcards
what are the major ecf osmoles?
Na+ and Cl-
what are the major ICF osmoles?
K+ salts
Regulation of ECF volume ≡
Regulation of body Na+
describe the distribution of body water?
what will changes in the content of Na+ cause?
changes in ECF volume and ∴ will affect the volume of blood perfusing the tissues = effective circulating volume and ∴BP.
what is regulation of Na+ dependent on?
high and low P baroreceptors.
what is the renal response to a decreased ECF volume?
(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.
effect of increased sympathetic discharge on the kidney?
↑ 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
Na+ reabsorption?
↑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.)
what maintains GFR and VC?
Autoregulation maintains GFR and the VC of afferent and efferent means little effect on GFR until volume depletion severe enough to cause considerable ↓ MBP.
what is the regulation of distal tubule Na+ reabsorption is under the control of?
adrenal cortical steroid hormone, aldosterone.
Very important in the long-term regulation of Na+ and ECF volume.
what are juxtaglomerular cells?
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
what is the macula densa?
They are closely associated with a histologically specialized loop of the distal tubule
The two together form the Juxtaglomerular apparatus.
what is aldosterone secretion controlled by?
Aldosterone secretion controlled by reflexes involving the kidneys themselves.
what do 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.
JG cells act as “renal baroreceptors”, less distension → ↑ secretion of renin. Intrinsic property, occurs if denervated.
what does renin do?
off the decapeptide angiotensin I which is then converted by enzymes in the endothelium to the active octapeptide = angiotensin II
what is ACE, where is it found?
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.
describe the role of angiotensin 2?
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.
what is the rate limiting step in conversion of angiotensin?
The rate limiting-step is the release of renin since angiotensinogen is always present in plasma.
what controls renin release?
↑ 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).
what is the relationship like between afferent arterioles and JG cells?
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.
describe the action of angiotensin 2 in hypovolaemia?
1.It stimulates aldosterone and ∴ NaCl and H2O retention.
- It is a very potent biological vasoconstrictor, 4-8 x more potent than NE, ∴ contributes to ↑ TPR
- It acts on the hypothalamus to stimulate ADH secretion → ↑ H2O reabsorption from CD.
- It stimulates the thirst mechanism and the salt appetite (in the hypothalamus).
what occurs in hypovolaemia?
↑ proximal AND distal tubule Na+ reabsorption together with osmotic equivalents of H2O, helps restore volume deficits, mediated by CV reflexes.
what contributes to GFR constancy?
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?
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.
when is volume consideration more important than osmolarity?
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.
lose water ______?
infuse or drink saline - lose water, replace salt and water
what does aldosterone promote?
Na+ reabsorption
what does ANP promote?
Na+ excretion
what happens if aldosterone is given to normal subjects?
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
what happens in patients with conns syndrome?
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.
why is osmotic diuresis important to consider in terms of hypovolaemia?
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
describe osmotic diuresus in an uncontrolled diabetic?
- Glucose remains in the tubule and exerts an osmotic effect to retain H2O in the tubule
- ∴ [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+.
- 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. - 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. - 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.
summarise the effects on uncontrolled diabetes on rebasorbtion of h20?
A large volume of nearly isotonic urine will be excreted → ↓ PV.
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.
