Blood volume regulation Flashcards
Glomerular Filtration rate equation
kidney function sensitive to changes in MAP
GFR
→ rate of fluid filtered from renal capilaries to bownman’s space
Kf
→ filtaeration coefficient (permeability cappilary is to water)
σ
→ Reflection coefficient (impermeabilty cappilary is to protein)
PGC
→ glomerular cappilary hydrostatic pressure
PBS
→ bowman’s space hydrostatic pressure
πGC
→ glomerular cappilary oncotic pressure
πBS
→ bowmans space oncotic pressure
(image)
What type of capillaries does the kidney have?
- fenestrated capillaries
- which gives an increased Kf
- so it has a high filtration rate
What is the glomerulus enveloped by?
Where is filtrate collected?
The glomerulus is enveloped by a layer of epithelial cells called the Bowman’s capsule.
The filtrate is collected into the tubular epithelium of the nephron.
Mean arterial pressure (MAP)
Mean arterial pressure set by cardiovascular system control blood flow into glomerular capillaries.
Kidney function is sensitive to changes in MAP.
GFR = Kf[(PGC-PBS) - sigma(piGC - piBS)]
If ↓ MAP:
- then not enough for glomerular filtration
GFR = glomerular filtration rate is the rate of fluid filtration from the renal capillaries into the Bowman’s space
Kf = filtration coefficient is the permeability of the capillary to water
Sigma = reflection coefficient is how impermeable the capillary is to proteins
How does the kidney filter the blood?
The kidney has:
- fenestrated capillaries
Increased ↑ filtration coefficient (Kf) is the primary cause of this high filtration rate.
Podocytes and basement membrane
→ Podocytes wrap around the glomerular capillaries
→ to create a barrier which prevents filtration of cells and proteins
→ The basement membrane helps select what can cross the filtration barrier based upon molecular weight and electrical charge
Response to upstage changes and control of blood volume
Rapid stabilisation of glomerular filtration rate is elicited by contraction of the afferent arteriole
1) Myogenic response of the afferent arteriole
2) Tubuloglomerular feedback
Auto-regulatory mechanisms:
- relative vascular resistance
- renal blood flow
- GFR
Myogenic response of the afferent arteriole (4)
1)
→ Increased arterial blood pressure
2)
→ stretch of vascular smooth muscle cells of afferent arterioles
→ activating stretch-sensitive Ca2+ permeable channels
3)
→ cytosolic Ca2+ rise
→ triggering smooth muscle cell contraction
4)
→ afferent arteriole vasoconstriction
→ and reduces renin secretion
The opposite series of events will also occur when arterial blood pressure is decreased.
Tubulogloreular feedback
→ upon increased arterial blood pressure
→ GFR increases
→ triggering increased fluid flow to the distal tubules
If we artificially increase fluid flow to the distal convoluted tubule we can see this triggers an afferent arteriole vasoconstriction.
This is the indirect mechanism and also causes renin inhibition.
Juxtaglomerular apparatus
→ communication between the afferent arteriole and the distal convoluted tubule happens at a specialised portion of the nephron called the Juxtaglomerular apparatus.
→ paracrine signalling between the afferent arteriole and distal convoluted tubule
→ specialised cells in the DCT called the Macula Densa sense the change in GFR
→ MDC sends paracrine message to the afferent arteriole
Tubuloglomerular feedback mechanism (high BP = high GFR)
1)
→ ↑ GFR
→ ↑ fluid flow to the DCT
2)
→ ↑ Na+ uptake into MDC
→ stimulates Adenosine release from the MDC
3)
→ Adenosine triggers vasoconstriction of afferent arteriole
→ reducing GFR
4)
→ Adenosine also inhibits renin secretion from granular cells
→ due to Ca2+ increase
Tubuloglomerular feedback mechanism (low BP = low GFR)
1)
→ ↓ GFR
→ ↓ fluid flow to the DCT
2)
→ ↓ Na+ uptake into MDC
→ stimulates PGI2 and NO release from the MDC
3)
→ PGI2 and NO trigger vasodilation of afferent arteriole
→ increasing GFR
4)
→ PGI2 and NO act on JXG cells to release Renin
→ Renin increases blood pressure
→ increasing GFR
What controls mean arterial pressure?
The Arterial Baroreflex:
→ the stiff arteries resist expansion, pressuring the blood pumped into it
(creating rapid flow to the tissues)
→ Mean Arterial Pressure reflects the second-to-second functioning of the cardiovascular system and is controlled by the Arterial Baroreflex
→ the compliant veins stretch to accommodate more blood being pumped into it
(acting as a blood reservoir which fills the heart)
→ 66% of total blood volume is stored within the systemic venous circulation
→ Venous Pressure is principally dependent on total blood volume
→ Cardiopulmonary baroreceptors - in aorta and great veins supplying the heart
(won’t change pressure inside veins)
Blood volume is a key determinant of MAP
Blood volume is a key determinant of MAP by ensuring sufficient venous return to the heart:
1) Decreased blood volume:
↓ venous pressure
↓ venous return
2)
↓ filling
↓ EDV (end diastolic volume)
3)
↓ cardiac output
(frank-starling mechanism)
4)
↓ MAP
The opposite for an Increased blood volume.
Restoring blood volume is essential in haemorrhaging patients to prevent shock.
Increasing blood volume
→ blood volume cannot be increased simply by drinking fluids
→ to increase blood volume, have to increase Na+ plasma content first
→ Osmoregulation is used to set blood volume
The kidneys regulate Na+ content by a variety of mechanisms
Decreasing blood volume will:
→ increase sympathetic tone
→ by cardiopulmonary baroreceptors
Decreasing blood volume will also:
→ decrease MAP
→ increasing sympathetic tone
→ by arterial baroreceptors
(Sympathetic tone inhibits kidney function)
The decreased MAP will also have intrinsic effects on kidney such as:
→ decreased urine Na+ excretion
→ activation of the renin-angiotensin- aldosterone system (RAAS)
Kidney responding to long term reductions in arterial blood pressure brought about reduced blood volume
Intrinsic mechanisms:
→ immediate response
→ weak so amplified by extrinsic mechanisms
→ stabilise GFR (trigger endocrine messengers)
Extrinsic mechanisms:
→ neural signalling - rapid onset, relatively transient, stabilise ABP (trigger endocrine messengers)
→ endocrine mechanisms - slow onset, maintained response, increased blood volume (maintain previous responses)
Intrinsic Responses to reduced blood volume
stabilise GFR and start to reduce urine output
Decreased blood volume → decreased arterial blood pressure →
1) Myogenic mechanism:
→ tubuloglomerular feedback
→ leading to stabilisation of GFR
OR
2) Pressure diuresis:
→ pressure natriuresis
→ leading to decreased urine output
OR
3) Myogenic mechanism:
→ tubuloglomerular feedback
→ leading to increase in renin secretion
→ as lower Ca2+ levels activates RAAS system
This all leads to:
→ maintaining excretion of nitrogenous wastes
→ and restoring blood volume.
3 main outcomes of intrinsic mechanisms for decrease blood volume and what it leads to
1) Stabilisation of glomerular filtration rate
2) Decreased urine output
3) Increased renin secretion
This all leads to mainting excretion of nitrogenous wastes and restoring blood volume
Pressure diuresis and natriuresis
→ increases in arterial blood pressure
→ reduces NaCl and water reabsorption by proximal tubule
→ increase urine output
→ (increase in water excretion and increase in sodium excretion)
→ returns blood volume to normal values (very slowly)
Neural signalling
Inputs:
- cardiopulmonary baroreceptors sense ↓ blood volume (eg. Haemorrhage) and ↓ venous pressure
- ↓ filling in the heart is sensed
- arterial baroreceptors sense ↓ MAP
Outputs:
- ↑ thirst and ↑ Na+ appetite
- ↑ in sympathetic signals → ↑ Na+ reabsorption
- ↑ ADH secretion → ↑ H2O reabsorption
- ↑ adrenal gland secretion → ↑ arteriolar vasoconstriction
- ↑ cardiac output and ↑ arteriolar vasoconstriction
This all helps to stabilise MAP and restore blood volume
How increased sympathetic nervous system increases Na+ reabsorption
…by the kidney
Decreased blood volume:
→ detected by cardiopulmonary and arterial baroreceptors
→ increased sympathetic firing frequency
1) Increased proximal tubule Na+/H+ exchange
AND
2) Vasoconstriction of arterioles (efferent > afferent)
AND
3) Increased renin secretion
All leads to increased Na+ reabsorption
How noradrenaline increases Na+ reabsorption from the proximal tubule
1) Noradrenaline upregulates Na+/H+ exchange activity in the proximal tubule
(H+ and Cl- out)
(Na+, glucose and amino acids in)
2) Vasoconstriction of both arterioles (efferent > afferent)
A.
Maintain GFR:
→ afferent contraction slows blood flow into glomerular capillaries (-)
→ Efferent > afferent contraction
→ increased proportion of plasma filtered (increase filtration fraction)
→ Increases colloid osmotic pressure in peritubular capillaries (+)
B.
Increase Na+ reabsorption:
→ Efferent > afferent contraction
→ increased proportion of plasma filtered (increase filtration fraction)
→ Increases colloid osmotic pressure in peritubular capillaries
→ Efferent and afferent contraction reduces peritubular capillary pressure
Isosmotic fluid reabsorption modulation
→ isosmotic fluid reabsorption from the proximal tubule can be modulated by altering Starling’s forces across the peritubular capillaries
→ favours reabsorption of interstitial fluid into peritubular capillaries
→ the lower renal intestinal pressure, favouring further water and NaCl reabsorption from tubule
Endocrine mechanisms
(Decreased blood volume)
Decreased blood volume:
→ decreased stretch of afferent arteriole, decreased flow to macular densa, increased sympathetic outflow
→ kidney increases renin secretion
→ renin converts Angiotensin from the liver to Angiotensin I in pulmonary circulation
→ ACE converts Angiotensin I to Angiotensin II which returns back to systemic circulation
→ causes adrenal gland to release Aldosterone
Role of Angiotensin II
Angiotensin II maintains the effects of the sympathetic nervous system on the kidneys
Decreased blood volume:
→ increased angiotensin II concentration due to the action of renin (angiotensin II maintains everything long term)
- increased arteriolar vasoconstriction leading to increased MAP
AND
- Increased thirst and Na+ appetite leading to increased Na+ and water intake
AND
- Increased Na+ reabsorption
→ ↑ proximal tubule Na+/H+ exchange
→ Vasoconstriction of arterioles (efferent > afferent)
→ ↑ aldosterone secretion
Aldosterone
Aldosterone:
→ increased Na+ reabsorption
→ from the principal cells of the distal nephron
→ Angiotensin-2 acts on adrenal cortex
→ on zona glomerulosa
→ leading to Aldosterone secretion
→ Aldosterone acts on DCT to make it more permeable to Na+ and H2O
→ ↑ blood volume = ↑BP = ↑GFR
The timeline of response to haemorrhage
1) Seconds
→ stabilise arterial blood pressure with baroreflex
2) Seconds
→ neuroendocrine reflexes elicit increases in plasma [catecholamine], [ADH] and [Ang II]
→ elicit arteriolar vasoconstriction
3) Minutes
→ reduction in starling’ forces allows net reabsorption of fluid from interstitial fluid into plasma (trans capillary refill)
4) Hours
→ stabilisation of circulation volume by increasing renal sodium and water reabsorption mediated by angiotensin II, aldosterone, ADH and renal sympathetic nerves
5) Hours
→ increased thirst and sodium appetite stimulated by baroreceptors and angiotensin II
6) Days
→ increased production of albumin, erythrocytes and platelets
Atrial natriuretic peptide
[opposite effect of AT-2]
Atrial natriuretic peptide is secreted from atrial myocytes in response to increased blood volume.
Increased blood volume:
→ (stretch of atrial walls)
→ increase in atrial natriuretic peptide secretion
1) Decrease proximal and distal tubule Na+ transport
AND
2) Vasodilation of arterioles (afferent > efferent)
AND
3) Inhibits renin and aldosterone secretion
All leads to decreased Na+ reabsorption and decreased blood volume
