Lecture 5.1: Renal Control of Volume and Blood Pressure Flashcards
What is included in Extracellular Fluid (ECF) Volume?
• Intravascular Volume
• Interstitial Fluid Volume
What is the clinical presentation of too much ISF?
Oedema
Where is most of the blood in the body?
• Most blood is in the veins
What is Frank-Starling’s Law?
• Cardiac Output = Stroke Volume x HR (Where
SV = EDV-ESV)
• End Diastolic Volume (EDV) & End Systolic
Volume (ESV)
• i.e. more in → more out
“For a given level of vascular capacity, the ‘fullness of the circulation’ and the rate of venous return vary directly with the volume of blood”
What happens to venous pressure if blood volume increase?
It increases
What effect will increased venous pressure have on cardiac output?
Increases cardiac output
What is Blood Pressure (BP)? What is a normal reading?
• Force exerted by blood against vessel walls
• Less than 120/80 mmHg
What is the Mean Arterial Pressure Equation?
Mean arterial pressure = cardiac output x total peripheral resistance (TPR)
What is BP influenced by? (5)
1) Cardiac factors: volume of blood from left ventricle contraction
2) Peripheral resistance: arteriolar diameter, which is variable
3) Blood volume: total volume of blood (i.e. cells and plasma) if blood volume ↓
BP ↓
4) Viscosity: ↑ blood viscosity causes greater resistance to flow and therefore ↑
arterial pressure
5) Arterial elasticity: when the elasticity of larger arteries ↓, resistance ↑, and
therefore systolic pressure ↑
Why do the kidneys require a stable mean arterial blood pressure?
• The kidneys require a stable mean arterial blood pressure to maintain GFR (i.e.
BP must not be too high nor too low)
Why must GFR remain constant? What rate?
• To maintain renal function and prevent renal damage
• Approx. 120 ml/min/1.73 m2)
What mechanism is the GFR maintained by?
• Autoregulation (see Session 3)
How is Blood Pressure Regulated?: Short Term
• Autonomic Regulation
• Baroreceptor Reflex
• Respond to Vascular Stretch (see CVS Unit)
• Adjust sympathetic input to peripheral resistance vessels to alter TPR
• Adjust sympathetic and parasympathetic inputs to the heart, to alter cardiac
output
How is Blood Pressure Regulated?: Long Term
• Extracellular Fluid Volume
• Renin Angiotensin-Aldosterone System (RAAS)
What organ is primarily responsible for maintaining BP long term? How?
• The kidneys primarily control long-term BP by
controlling the amount of Na+ in the ECF
How many grams of sodium does WHO recommend a limit of?
2g/day
Obligatory Reabsorption of Na+ in PCT: Percentage? How?
• 65% of filtrate
• Basolateral Na+/K+-ATPases and luminal Na+ channels (e.g. ENaCchannels and
SGLT2 co-transporters)
Obligatory Reabsorption of Na+ in TAL of the Loop of Henle: Percentage? How?
• 25%
• Na+/K+/2Cl- co-transporter
Variable Reabsorption of Na+ in Distal Tubule: Percentage?
• Up to 8%
Variable Reabsorption of Na+ in the Outer Medullary Collecting Duct: Percentage?
• Up to 3%
What percentage of Na+ is excreted in the urine?
• c.0.4%
What percentage of Water is Reabsorbed in the Proximal Tubule?
• 65%
What percentage of Water is Reabsorbed in the Descending Thin Limb of the
Loop of Henle?
• 15%
What percentage of Water is Reabsorbed in the Collecting Duct?: Water-Loading and in Dehydration
• 5% (during water-loading)
• >24% (during dehydration)
Thick Ascending Limb (TAL) (late segment): Ion Movement [Transporters]
• The Na+/K+/2Cl- co-transporter ‘dilutes’ the tubular fluid by moving Na+/K+/2Cl
into the tubular epithelium of the TAL
• K ions then diffuse back via the renal outer-medullary potassium channel
(ROMK) into the tubular lumen to maintain Na+/K+/2Cl- co-transporter activity
• The return of K maintains a positive charge in the TAL lumen, allowing the
paracellular reabsorption of Na+, Ca2+ and Mg2+from the TAL.
What is the role of Loop Diuretics such as Furosemide (in regards to TAL)
Loop diuretics, such as furosemide, block the Na+/K+/2Cl- co-transporter by competing for Cl-
Distal Convoluted Tubule Transporters
Na+/Cl- enter across apical membrane via the electroneutral NCC transporter (Sodium-chloride symporter)
What Hormones and Diuretics is the NCC Transporter sensitive to?
• Thiazide diuretics
• Parathyroid hormone
• Calcitriol/Vitamin D3 (stimulate Ca2+ reabsorption via apical Ca2+ channels,
and a Vitamin D3-dependent protein)
What type of cells make up the majority of the distal nephron?
Principal Cells
What transporter/channel on Principal Cells is responsible for water reabsorption?
• Reabsorption of water via AQP-2
What transporter/channel on Principal Cells is responsible for Na+ reabsorption?
• Principal cells reabsorb 2-3% of total filtered Na+ions via ENaCs (epithelial Na+
channels)
What hormone promotes ENaC expression?
• Aldosterone promotes ENaC expression
• Allowing maximal Na+ reabsorption during volume depletion
What diuretic blocks ENaC?
Amiloride is a ‘K+-sparing’ diuretic that acts by blocking ENaC
Na+ moves without Cl- in the ENaC inhibitor, what effect does this have on the lumen of the collecting ducts?
Here, Na+ moves without Cl-, making the lumen more negatively charged, thereby promoting the electrogenic secretion of K+ via selective K+ channels
What sensors are involved in regulating ECF volume? (3)
• The Juxtaglomerular Apparatus (JGA)
• The Atria
• The Carotid Sinus
What are Effector Mechanisms?
Mechanisms that respond by altering Na+ excretion and systemic vascular resistance
Sensors involved in Regulation of Volume: The Juxtaglomerular Apparatus (JGA)
The granular cells of the JGA release renin in response to low BP, thereby initiating the renin-angiotensinaldosterone system (RAAS)
Sensors involved in Regulation of Volume: The Atria
They release natriuretic peptides to promote Na+ excretion
Sensors involved in Regulation of Volume: The Carotid Sinus
Regulates the activity of the sympathetic nervous system, and relays the hypovolemic stimulus to vasopressin
What is the process of Renin release from Juxtaglomerular Apparatus (JGA) ?
• In response to ↓ BP, the biologically-inactive precursor (prorenin) within the
granules of the granular cells is cleaved to form renin
• The active enzyme renin is then released from the granular cells that surround
the afferent arteriole, into the circulation (T1/2 80 minutes)
What is the role of Renin?
Renin’s only known function is to cleave angiotensinogen (renin substrate), to form angiotensin I
What is Angiotensin (II)?
Angiotensin is a hormone that helps regulate your blood pressure by vasoconstriction and triggering water and sodium intake
Regulation of Renin Secretion: Stimulation (3)
• Low BP (sensed by cardiopulmonary baroreceptors) triggers sympathetic
stimulation & catecholamine release to stimulate β1 receptors in JGA
• Low BP (sensed by afferent arteriole baroreceptors) stimulates local release of
prostaglandins
• Increased sympathetic activity via renal nerves
Regulation of Renin Secretion: Inhibition (4)
• Increased Na+/Cl- reabsorption by the macula densa cells of the early distal
tubule
• Elevated BP in the afferent arteriole
• Angiotensin II (Negative-Feedback)
• Vasopressin
How is Angiotensin II formed? What effect does it have on the Kidneys and BP? (6 Steps)
• Angiotensinogen (453 aa protein formed by the liver)
• Renin the cleaves this into Angiotensin I
• Angiotensin-Converting Enzyme (ACE) converts this to Angiotensin II (active)
• Angiotensin II stimulates Aldosterone release (from adrenal cortex)
• Aldosterone causes increased Na+ absorption in kidneys (direct and indirect)
• ↑ ECF Volume ↑ systemic BP
Effect of Aldosterone on Sodium uptake?
• Released from the zona glomerulosa (a mineralocorticoid)
• Causes sodium to be absorbed and potassium to be excreted into the lumen
by principal cells
• Acts on the cells of the DCT and cortical collecting duct by stimulating the
expression of ENaC channels
If BP rises too much due to Renin, what hormone stimulates a decrease in BP?
Atrial Natriuretic Peptide (ANP)
Where is Atrial Natriuretic Peptide (ANP) produced? How does it work?
• Heart Atrial Cells
• ANP inhibits expression of ENaC channels in the principal cells
• ANP block Renin secretion
• This reduces Na+ reabsorption from the connecting tubules/collecting ducts
• Thus causing ↓ ECF volume and ↓ BP
