ECF Volume Regulation 1 Flashcards
What is the distribution of total body water between cels are ECF determined by?
The number of osmotically active particle in each compartment
Name the important osmotically active particles in each compartment
- 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)
How does Na effect distribution of water?
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
What is he regulation of Na dependent on?
High and low pressure baroreceptors
What are the steps in Na effecting high and low presser barorectors?
↑ 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
What stimulated the ADH secretion in loss of decreased plasma?
Decrease firing of low and high pressure baroreceptors
What is the effect of vasoconstriction in the sympathetic nervous system response to decreased plasma volume?
Vasoconstriction in the renal arteries -> ↑ renin release
What is the function of renin?
Regulates water and Na reabsorption by the kidney -> release of angiotensin II -> increase reabsorption directly on prox. Tubule and indirectly of distal tubule.
What is the effect of increased sympathetic discharge (due to low plasma volume) on the kidney?
↑renal VC nerve activity -> ↑ renal arteriolar constriction and an ↑ in renin
What is the effect of increased renin in response to increased sympathetic discharge?
↑ 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.
What allows an ↑ Na reabsorption from proximal tubule in response to increase sympathetic discharge?
Greater reabsorptive forces in peritubular capillaries (↑ oncotic and ↓ hydrostatic p)
What is the reabsorptive range of Na in the proximal tubule?
65% in volume excess to 75% in volume deficit (range due to changes in starling’s forces)
How does the GFR remain unchanged?
Autoregulation maintains GFR and the vasoconstriction of afferent and efferent means little effect on GFR until volume depletion severe enough to cause considerable ↓ MBP
What is the physiological response of the kidney to hypovolemia?
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
What is the physiological response of the kidney to hypervolemia?
PPC > normal therefore efferent arteriole is less constricted and oncotic p < normal therefore plasma proteins are diluted by retention of salt and water
What is Na reabsorption from the distal tubule controlled by?
Aldosterone
What is the specialisation of afferent arterioles to maintain Na content?
Smooth muscle of the media of afferent arterioles contains large epithelial cells; Juxtaglomerular cells (JG) which monitor pressure and Na content
What two structures form the juxtaglomerular apparatus?
Juxtaglomerular cells and the macula dense (specialised loop of distal tubule)
How is the juxtaglomerular apparatus structured?
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.
How is renin activated?
Low BP detected by the juxtaglomerular apparatus
What produces renin?
JG cells
What is renin?
A proteolytic enzyme which acts on a large protein in the alpha2-globulin fraction of the plasma proteins = angiotensinogen
What is the function of renin?
Converts Angiontensinogen -> angiontensin I (and ACE converts angiotensin I -> angiotensin II)
Rate limiting step is concentration of renin; more renin, more angiontensin II produced
What is the function of angiotensin II?
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.
List the effects of angiotensin II
- Arterioles -> vasoconstriction
- Kidneys -> Na reabsorption
- Sympathetic NS -> increase release of noradrenaline
- Adrenal cortex -> release of aldosterone
- Hypothalamus -> increases thirst and ADH release
What controls the release of renin?
- 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
Wh tis angiotensin II important in the body’s repose to hypovolemia?
- It stimulates aldosterone and therefore NaCl and H2O retention in the blood.
- It is a very potent biological vasoconstrictor, 4-8 x more potent than noradrenalin, therefore 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 is the tubuloglomerular feedback?
Mechanism used to regulate GFR
How does the tubuloglomeular feedback system work?
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
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?
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
What is more important in emergency situation (wrt ADH release) if osmolarity is decreased in ECF, but insufficient volume?
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.
What is the main determinant of [ADH]?
Osmolarity of ECF
