ECF volume regulation Flashcards
Name the 2 major osmoles of the ECF (osmoles = osmotically active solutes, i.e. non freely penetrating solutes that require movement of water to equilibrate the osmotic pressure)
Na+ and K+
Regulation of ECF volume essentially relies on regulation of what non penetrating solute
Na+
Total body water (42L) is distributed into what 2 compartments
ECF - 1/3
ICF - 2/4
ECF makes up what fraction of total body water + what is ECF further divided into
1/3
Plasma - 3L
ISF - 11L
ICF makes up what fraction of total body water
2/3
What’s bigger - ECF or ICF
ICF
Hypovolaemia =
blood volume loss, i.e. decreased ECF
Hypovolaemia decreases plasma volume which consequently causes what following things to be decreased
↓PV ↓Venous pressure ↓Venous return ↓atrial P ↓EDV ↓SV ↓CO ↓BP ↓carotid sinus baroreceptor discharge as it can sense less stretch of the vessel
Hypovolaemia causes decreased BP which leads to a decrease in carotid sinus baroreceptor discharge (as it senses less stretch from low BP so decreases discharge rate)
What are the different sympathetic responses of the body to this
Medullary cardiovascular centre receives this info and stimulates sympathetic nerves
innervating
- SA node to release NA, acting on the node to depolarise it faster and increase HR to pump more blood around body
- veins to constrict to squeeze spare capacitance of blood back to heart –> increase VR –> increase EDV –> increase preload –> increase contraction strength –> increase CO –> increase BP
- arterioles to constrict –> increasing total peripheral resistance –> in order to increase MAP back to normal
Long term control of BP is controlled by what 3 things
Renin-angiotensin-aldosterone system
ADH
Atrial natriuretic peptide (ANP)
What is sympathetic response of the kidneys to hypovolaemia (or low BP)
Sympathetic nerves innervating it release NA which bind to the a1 receptors of the arterioles and CONSTRICT them –> increasing TPR –> increasing MAP
The sympathetic response of the kidneys to low BP or hypovolaemia is to constrict their afferent arterioles in order to increase TPR and therefore increase MAP
What detects constriction of the renal arterioles and what is subsequently activated from this
Juxtaglomerular cells sense decreased distension of the afferent arteriole and causes increased secretion of renin
What cells produce renin
juxtaglomerular
What does renin do
Convert angiotensinogen to angiotensin I
What does angiotensin converting enzyme (ACE) do
convert angiotensin I to II
Functions of angiotensin II towards the kidney (2)
Stimulates release of aldosterone –> increases Na+ reabsorption in the distal tubule so reduces diuresis
Increases Na+ and water reabsorption in the proximal tubule so less diuresis
Aldosterone increases sodium and water reabsorption in the proximal or distal tubule
distal
Main driving force of reabsorption into the peritubular capillaries
oncotic pressure
Reabsorptive range in proximal tubule is 65-75%, how does this differ in times of volume excess or volume deficit (hypovolaemia)
if volume excess, nearer 65%
if volume deficit, nearer 75%
Reabsorption from proximal tubule to peritubular capillary is largely driven by what
starling’s forces, specifically oncotic force as that’s driving the fluid to move into the peritubular capillary
Does volume depletion affect GFR
Only if volume depletion severe enough to decrease MAP significantly
If not, autoregulation maintains it through constricting its arterioles
In hypervolaemia, is the peritubular hydrostatic pressure and oncotic pressure increased or decreased
increased
decreased
In hypovolaemia, is the peritubular hydrostatic pressure and oncotic pressure increased or decreased
decreased
increased - in order to reabsorb as much water back as possible
What maintains GFR in times of low BP
Constriction of afferent arteriole due to sympathetic activity
Constriction of efferent arteriole due to angiotensin II acting on it
Distal tubule na+ reabsorption is controlled by what hormone
aldosterone
What is the macula densa/function + where is it
area of closely packed specialised cells lining the wall of the distal tubule and senses changes in NaCl conc. in the tubul and triggers autoregulatory response to increase/decrease reabsorption of Na+
Where are the juxtaglomerular cells that secrete renin
in the afferent arteriole
Rate limiting step of the renin-angiotensin-aldosterone system
release of renin by the juxtaglomerular cells since angiotensinogen is constantly present in plasma
Renin release triggered by (3)
Decreased distention/pressure of afferent arteriole
Activation of sympathetic nerves innervating the juxtaglomerular cells via NA acting on b1 receptors
Decreased delivery of Na+ and Cl- through the tubule
Renin release inhibited by (2)
Angiotensin II feeding back on it
ADH
Summary of renal responses to hypovolaemia (2)
Increased renin –> increased angiotensin II
- decreases peritubular capillary hydrostatic pressure –> increasing Na+ reabsorption in proximal tubule
- stimulates aldosterone production –> increases distal tubule Na+ reabsorption
Effects of angiotensin II (4)
Stimulates aldosterone release
Potent vasoconstrictor –> increases TPR –> increases MAP
Stimulates ADH release
Stimulates thirst mechanism and salt appetite
If GFR increases, what is the intrinsic response of the kidney to counteract this
constrict afferent arteriole to decrease hydrostatic pressure
What effect does the following have on ADH release:
- decreased ECF osmolarity
- decreased ECF volume
decreased via OSMORECEPTORS
increased via BARORECEPTORS
Main determinant of ADH conc. at any given time?
But if there’s a big volume change that would compromise brain perfusion, then what becomes the primary determinant of ADH conc.
(i.e. these are triggers of ADH release/inhibition of release)
ECF osmolarity
ECF volume - as brain perfusion more important than disturbed osmolarity
Function of ANP
Increase excretion of Na+ (natriuresis) and therefore diuresis
- Renin-angiotensin-aldosterone system
- ADH
- Atrial natriuretic peptide (ANP)
are long term controls of BP, what is different about ANP from the other 2
ANP stimulates diuresis (i.e. excretion of sodium and water) while the other 2 do the opposite
What triggers ANP release from myocardial cells in the atria
Distension of the atria (i.e. higher BP)
Aldosterone causes secretion of what into the distal tubule
K+
Hyperaldosteronism would cause hypo or hyperkalaemia
Hypo because aldosterone stimulates K+ secretion into distal tubule to be secreted out
Why does hyperaldosteronism (e.g. conn’s syndrome) not cause hypernatraemia if aldosterone stimulates Na+ reabsorption
Because the increased blood volume caused by the Na+ reabsorption stretches the atria which triggers ANP release from atrial myocardial cells to cause increased natriuresis (excretion of sodium in urine)
In uncontrolled DM, BG conc. exceeds the maximum reabsorptive capacity in the proximal tubule so remains in the tubule which has what effect on water
Since it has this effect on water, the conc. of what cation decreases in the lumen
causes water to stay in tubule as well
Na+ because it’s diluted in a large volume of water
In hyperglycaemia, excess glucose is retained in tubule as maximum capacity is already reabsorbed which creates an osmotic effect and causes water to be retained as well
This causes Na+ conc. to decrease in the tubule as it’s diluted in more water so what effect does this have on Na+ reabsorption and glucose reabsorption
both decrease as Na+ conc. inside the lumen is decreased so the conc. gradient that it passively diffuses down from the lumen to the proximal tubule cell is reduced
glucose shares a symporter with Na+ therefore its reabsorption will be reduced too
Summarise the process of how hyperglycaemia in diabetes mellitus causes osmotic diuresis (4)
Glucose remains in tubule so exerts osmotic effect to retain water in tubule
Retaining water therefore decreases Na+ conc. in tubule so less passive sodium reabsorption in the proximal tubule as well
In the descending limb, water movement out into the interstitium reduced because of the osmotic effect that glucose and excess Na+ exert to retain water –> so diluted fluid is sent to the ascending limb and since NaCl pumps in the ascending limb are gradient limited, the medullary interstitial gradient is REDUCED so much less reabsorption of NaCl into the interstitium
-so altogether decreased loop of henle reabsorption
Therefore large volume of isotonic urine produced a day
If there’s increased delivery of NaCl and water to the distal tubule, the macula densa cells detect this and subsequently do what to help this
inhibit renin secretion in order to decrease Na+ reabsorption at the distal tubule and excrete the excess Na+
In hyperglycaemia in uncontrolled DM, the medullary interstitial gradient is abolished which causes osmotic diuresis (i.e. excrete large volumes of urine a day)
This therefore decreases plasma volume which would be detected by baroreceptors and they would stimulate ADH to reabsorb water in the CD but why won’t ADH work in these uncontrolled diabetics
because the medullary interstitial gradient doesn’t exist, fluid in the collecting duct is isotonic with the fluid around it so increased ADH won’t have much affect as there needs to be a gradient for water to be reabsorbed
How does a hyperglycaemic coma work - usually you hear more about hypoglycaemic comas because of reduced glucose to brain but why can high glucose cause a coma
because high glucose causes osmotic diuresis so lose a lot of water in urine which decreases plasma volume so in very severe circumstances, may reduce blood flow to brain
