CVS Lecture 9/10 - SNS and Renin-Ang-Aldosterone system and Microcirculation Flashcards
What is the ANS cardiovascular control?
Hypothalamic autonomic centre receives information from baroreceptors in the carotid sinus and the cardiac baroreceptors; PSNS= CNX
What is the main function of the SNS control of the heart?
To regulate BP -> fall in BP=SNS activation, vasoconstriction and PSNS inhibition so increased CO
What is the NT released from SNS?
Preganglionic = ACh; postganglionic = Noradrenaline -> adrenal medulla releases adrenaline
What occurs at a post ganglionic SNS synapse?
Either NA is taken up and recycled in presynaptic neuron or broken down in postsynaptic neurone
How is neurotransmitter released from the presynaptic membrane?
Granular vesicle fuses with varicosity membrane, opening the exocytotic channel, vesicle contents expelled by exocytosis -> NT taken up again and biosynthesis replenishes granular contents -> ACTIVE process
How is noradrenaline synthesised?
How is NA taken up from the synapse?
Neuronal uptake or extraneuronal uptake
What are the 2 effects of adrenoceptors?
Excitatory effects on SM -> alpha-adrenoceptor mediated; Relaxant effects on SM, stimulatory effect on heart -> beta-adrenoceptor mediated
What are the subdivisions of beta-adrenoceptors?
B1 -> located on cardiac muscle, SM of GIT; B2 -> bronchial, vascular and uterine SM; B3 -> fat cells and maube SM of GIT (thermogenesis involvement but few in humans)
What are the subdivisions of alpha-adrenoceptors?
A1 -> located postsynaptically and are important in mediating constriction of resistance vessels in response to sympathomimetic amines. A2 -> presynaptic (some post VSMC) and activation by released transmitter causes negative feedback inhibition of further transmitter release
How are alpha 1-adrenoceptors coupled?
Activated via agonist, then activates through G-proteins PLC which breaks down lipids releasing DAG and IP3, releasing Ca2+ into cytoplasm, activating PKC
How are alpha 2 and beta adrenoceptors coupled?
Beta activates adenylyl cyclase via G-proteins, causing increased cAMP, which is a negative system (not in the heart) -> A2 receptors inhibit adenylyl cyclase, reducing cAMP, increasing effect of intracellular Ca
Which adrenoreceptors interact with NA, adrenaline, DA, isoprenaline, phenylepinehrine?
NA: alpha 1 and 2, beta 1. Adrenaline: alpha 1 and 2, beta 1 and 2. DA: weak effects at alpha and beta 1 but has its own receptors. Isoprenaline: beta 1 and 2. Phenylepinephrine: alpha 1
What are the CV effects when patients are given NA, adrenaline or isoprenaline?
Why does NA cause these CV effects?
SV increases so SBP goes up, DBP goes up because of vasoconstriction (greater TPR, which leads to increase of MBP), HR decreases due to reflex bradycardia (constriction in periphery, activating baroreceptors, so decreasing HR)
Why does adrenaline cause these CV effects?
Some direct effect on the heart so increases HR, BP -> reduces DBP because dilates peripheral blood vessel -> MBP goes up a little (less than NA) and HR increases
Why does isoprenaline cause these CV effects?
Unselective beta-agonist; increases SBP a little, because it has direct effect on heart to increase contractility (positive ionotropic effect); reduces DBP because it has a potent vasodilator effect in periphery, so MBP remains unchanged or lowers slightly. HR goes up quite a bit, due to direct effect on the heart
What are the effects of NA, adrenaline and isoprenaline on skin, visceral, renal, coronary and skeletal muscle?
How does the RAAS work?
How is Ang II synthesised?
What factors regulate renin release?
Decrease Na reabsorption, BP low, increase beta-1 receptor activation
What occurs when BP falls in the RAAS?
Increase in beta-1 activity
How do we manipulate renin release?
What is the Ang II Type 1 receptor?
G-protein coupled, also coupled to PLA2 -> located in heart, kidney, blood vessels, brain, adrenal
What happens when AT1 receptor is activated?
Works to increase BP, harmful on peripheral blood vessels and probably on myocytes
How does Ang II cause peripheral resistance?
Direct vasoconstriction, enhanced action of peripheral NA (increased release, decreased uptake), increased SNS discharge, release of catecholamines from adrenal -> all leading to a rapid pressor response
What are the effects of Ang II in renal function?
Direct effects to increase Na reabsorption in PCT, synthesis and release of aldosterone from the adrenal cortex, altered renal haemodynamics (renal vasoconstriction and enhanced NA effects on kidney) -> slow pressor response
What are the effects of Ang II on CV structure?
Haemodynamic effects: increased preload and afterload, increased vascular tension; Non-haemodynamic effects: increased expression of proto-oncogenes, increased production of growth factors, increased synthesis of ECM proteins -> vascular and cardiac hypertrophy and remodelling
What are chymases?
Make Ang II from Ang I/Ang which are not inhibited by ACE inhibitors
What are the 2 functions of ACE?
Make AngII from Ang I and inactivate bradykinin -> ACE inhibitors cause the build up of bradykinin which is a vasodilator, so vasodilation occurs
What are the effects of AT1 receptor antagonists?
No effects on bradykinin system (which ACE inhibitors have), selectively block effects of Ang II -> pressor effects, stimulation of NA system, secretion of aldosterone, effects on renal vasculature, growth promoting effects on cardiac and vascular tissue
What is the effect of aldosterone?
Maintains body content of Na, K, H2O -> increased Na retention (and H2O), and increased K excretion (and H+)
What regulates aldosterone release?
ACTH (minor), AngII, high K+ levels in the blood
Where are aldosterone receptors located?
Kidneys, brain, vessels, heart
What are the effects of impaired aldosterone regulation (increase in aldosterone)?
What does stress cause the sympathoadrenal system and RAAS to do?
Increased BP, HR, Na/H2O retention, coagulation, platelet activation; decreased fibrinolysis
What is the microcirculation?
Circulation for each individual organ/tissue in the body
How is the microcirculation organised?
What is blood flow rate?
Volume of blood passing through a vessel per unit time
How is flow measured?
Pressure gradient/vascular resistance
How do we determine the flow rate of blood to a particular capillary bed?
The pressure in the arteriole compared to the pressure in the capillary creates a pressure gradient which determines the amount of blood flow -> Increased pressure gradient = increased flow rate
What affects resistance to blood flow in vessels?
Blood viscosity, vessel length, vessel radius -> R=1/r^4
What does increased BP cause to delta P, resistance and flow?
Delta P = increases, flow increases
What does vasoconstriction cause to delta P, resistance and flow?
Resistance increases, flow decreases
What are the arterioles?
Major resistance vessels -> with MAP the same in every tissue, and pressure in capillaries changes depending on the tissue
What is flow to any tissue in the body dependent on?
Since MAP is equal to pressure gradient (as there is very little pressure at the other end of the capillary), then flow is basically dependent on the resistance in that organ -> so the tissues determine how much blood flows to it
What can the arterioles do?
Determine blood flow to that tissue -> Vasoconstriction reduces flow, vasodilation increases flow
Why do most arterioles at rest display state of vascular tone (partial constriction)?
Needs to be partially constricted so that it can control flow in either direction
What are the 2 functions of arterioles which need independent adjustment of arterioles?
1) Match blood flow to metabolic needs of tissues -> regulated by local controls, independent of nerves or hormones. 2) Help regulate arterial BP, regulated by extrinsic controls
How can arterioles by locally regulated?
Active hyperaemia -> chemical: increased metabolism causes increased O2 usage which sends signal for vasodilation. Physical -> decreased blood temperature causes diversion of blood away from peripheries to prevent core body temp from decreasing. Myogenic vasoconstriction -> stretch causes the vessels to constrict to autoregulate flow when BP increases
How do the arterioles help to regulate arterial blood pressure?
By controlling TPR we can control BP -> Neural: medulla (CV control centre) sends signal to vasoconstrict heavily in certain tissues for rapid increase in BP. Hormonal -> Vasoconstrictors (VP, AngII), or increase SNS by stimulating adrenaline/NA release which cause vasoconstriction
Which tissues are going to constrict or dilate in response to neural stimulation to change BP and what does it depend on?
Depends on the receptors present in that tissue: alpha receptors -> constrict; Beta-receptors relax
How are arterioles controlled to vasodilate/vasoconstrict?
Intrinsic -> chemical (metabolic activity), physical (stretch) which match blood flow to metabolic need. Extrinsic -> neural (SNS output), hormonal (adrenaline, VP, ATII) which regulate arterial BP
What is the function of capillaries?
Capillary exchange -> delivery of metabolic substrate to the cells of the organism -> 1 cell thick, heavily branched
How are capillaries designed to enhance diffusion?
Minimise -> diffusion distance. Maximise -> SA, diffusion time
What is the importance of capillary density?
Different tissues have different capillary densities because it is dependent on higher metabolic activity -> lung isn’t metabolic demand, but for O2 extraction; heart and brain very dense networks. Skeletal muscle is highly perfused but most of the time is highly vasoconstricted, so very little blood flows through when no activity occurs
What is the structure of continuous capillaries?
Endothelial cells -> single cell thick-> small gap junction filled with H2O; MOST COMMON
What is the structure of fenestrated capillaries?
Endothelial cells with windows in the endothelial cell, which allows larger molecules to pass through -> glomerulus
What is the structure of discontinuous capillaries?
Very large gaps in capillary structure to allow larger molecules to pass through -> bone marrow
What is the blood brain barrier?
Capillaries with really tight gap junctions -> no water-filled ones; so nothing enters the brain unless it goes through the endothelial cells
How does fluid move across capillaries?
Bulk flow -> via the gap junctions. Hydrostatic pressure forces fluid out into interstitial fluid; oncotic pressure draws fluid into capillaries
What is bulk flow?
Volume of protein free plasma which filters out of the capillary, mixes with the surrounding interstitial fluid and is reabsorbed
What is Starling’s hypothesis about Starling forces?
Must be balance between hydrostatic pressure and oncotic pressure must be the same. If pressure inside capillary > in IF then ULTRAFILTRATION; if inward driving pressure > outward driving pressure then REABSORPTION
What are the different forces in the capillary at either end?
Oncotic pressure remains the same as the proteins remain in the plasma. Arteriolar end hydrostatic pressure is higher than oncotic so more fluid pushed out, venular end has decreased hydrostatic pressure, but oncotic remains the same so more water drawn back in
What is the significance that ultrafiltration is more effective than reabsorption?
There is a net loss of fluid -> which the lymphatic system brings back to the blood maintaining blood pressure
Where are lymphatic capillaries found?
Wherever there are vascular capillaries -> blind ended, not in a loop
What is the function of lymphatics?
Fluid drains in to lymph vessel, via little valves in between each cell
What is the function of lymph nodes?
To detect infection in the fluid
How is lymph flow maintained?
Needs other pressures -> thoracic pressures when breathing to draw fluid up
Where does lymph drain?
Right lymphatic duct, thoracic duct, R/L subclavian veins -> 3L/day is drained
What is oedema and how can it be caused?
When rate of production is greater than rate of removal of fluid in the tissues -> parasitic blockage of lymph nodes: Elephantiasis
