Cardiovascular System Flashcards
Complete Darcy’s Law.
Flow =
Difference in Pressure ÷ Resistance
Blood Pressure =
CO X TPR
SAN Pacemaker Potentials. Outline
Stage 4
Stage 0
Stage 3
4 - If Na+ channel activated by hyperpolarisation
0 - VGCa2+C open, rapid depolarisaton
3 - VGK+C cause K+ efflux and repolarisation
Atrioventricular APs. Outine Stage 4 Stage 0 Stage 1 Stage 2 Stage 3
4 - RMP maintained by Na/K pump
0 - VGNa+ open, Na influx, VGCaC start to open
1 - peak of AP, VGNa+ close
2 - VGCaC still open, VGK+C open - plateau phase
3 - VGCaC close, K+ effluxing so rapid repolarisation
P wave of an ECG shows?
Atrial Depolarisaton
T wave of an ECG?
Ventricular Repolarisation
Stroke Volume =
EDV-ESV
about 120-40 = 80ml
Ejection Fraction =
SV ÷ EDV
A wave of jugular venous pressure is due to
Atrial Contraction
X descent and Y descent can be seen as pulsatile collapse in the neck veins. What do these correspond to?
X descent - ventricular contraction
Y descent - atria contraction when tricuspid valve opens
S1 lub is due to which valves closing?
Tricuspid/Mitral
Why do you get greater energy of contraction with greater muscle fibre stretch at rest?
Starlings Law
- less overlapping of myosin/actin
- less mechanical interference
- increased Ca2+ sensitivity and more cross bridge formation potential
Laplaces Law is determined by wall stress (S).
S =
P X ( r ÷ 2w )
Afterload = Pressure X ( radius ÷ 2xwall thickness)
Laplaces law means that a small ventricle, will have greater wall curvature, so more wall stress is directed towards….
and ejection is….
the centre so there is less afterload
and ejection is better
In a healthy heart Laplaces law facilitates ejection as during ventricular contraction, chamber radius decreases, reducing afterload and aiding ejection.
What happens in a failing heart?
Compensation
Effect on CO
What happens to S
- chambers are dilated so radius is higher, S increases.
- to compensate w is increased by hypertrophy
- this increases CO
- S is the same but is spread over a larger area
How does NA increase ionotropy?
- acts on B1 receptors
- GaS pathway, increases PKA
- phosphorylates VGCC and RyR
- increased Ca and CICR so increased force of contraction
Name 3 Negative Ionotropic Agents
- Hyperkalemia
- high H+/acidity as H+ competes for TnC sites
- hypoxia as leads to local acidosis ^
Arrythmias result from
-Abnormal impulse generation or
-Abnormal conduction
Give 2 examples of each
Impulse: -automatic rhythms/increased SAN activity
-Triggered rhythms: EAD, DAD
Conduction: -heart block
-re-entry electrical circuits
Two things anti-arrythmic drugs can target:
- reducing conduction velocity
- reducing automaticity
Anti-Arrhythmic Drug Classes act at: I II II IV
Do they act nodally, non-nondally or both at the node and non-nodally?
I - Na+ channel blockers (non nodal)
II - B blockers (both)
III - K+ channel blockers (non nodal)
IV - CCB (both)
How do Class III anti-arrhythmic drugs such as Amiodarone act?
Block K+ channels to maintain depolarisation.
Na+ channels are inactivated so the refractory period increases during which more APs cant fire
4 passive transport processes
- diffusion
- osmosis
- convection (Pressure)
- Electrochemical flux
What 4 things control the rate of solute transport?
- Passive diffusion properties (T = x2 / 2D)
- Properties of solvents and membranes
- Properties of capillaries
- Permeability
What are the three types of capillaries?
- continous (e.g. BBB)
- fenestrated (e..g. kidneys)
- discontinous
What is the glycocalyx?
A negatively charged material covering the endothelium which blocks solute permeation
What controls diffusion rate? 3 things
- blood flow (less time for equilibration of grad)
- decreased interstitial concentration (bigger difference)
- recruitment of capillaries (increases SA and shorter distance)
Starling’s principle of fluid exchange that balance between hydraulic and oncotic pressure regulates exchange, was revised to include the….
As…
Glycocalyx
As…plasma proteins move from the lumen to interstital space via a vesicle system not via intracellular spaces as the glycocalyx acts a barrier
Oedema results from promoted…
e.g. due to
Filtration
..increased Pc/ increased Lp (how leaky endothelium is) / increased πg / decreased πp
Give 2 examples of conditions where filtration is promoted due to decreased πp.
- Nephrotic Syndrome - urinary protein loss
- Liver disease - not enough albumin produced
Complete the equation for Bernoulli’s Law of blood flow
FLOW =
PRESSURE + KINETIC + POTENTIAL
pv + pv2/2 + pgh
Name 3 Types of Blood Flow
- Laminar (normal)
- Turbulent (not linear flow due to velocity changes)
- Bolus (in capilaries, single file, low R)
Reynolds Number:
Re = pVD/u
describes what?
Re = p-density Velocity Diametre / Viscosity
Describes change from laminar to turbulent flow
if Re > 2000 turbulent e.g. bruits, ejection murmur
Give 3 parametres that affect BP
- CO
- Properties of arteries
- TPR (arterioles)
- viscosity (Ht)
Pulse Pressure =
Systolic BP - Diastolic BP
about 120-80=40mmHg
or SV / Compliance
Compliance =
Change in Volume / Change in Pressure
Poiseulle’s Law
Conduction =
πr4 / 8nL
π radius4 / 8 viscosity length
Give 3 factors that control TPR
- radius^4, and length
- myogenic response
- blood viscosity
- pressure difference
Contrast bolus flow and flow in arterioles.
- bolus flow has low viscosity, and low resistance
- arterioles are arranged in series so total resistance is greater
Outline the Bayliss Myogenic Response
increase in distention of a vessel causes constriction
increased constriction in a vessels causes dilation
-maintains local flow during changes in BP
What three factors determine viscosity (n)?
- blood velocity
- vessel diameter
- haematocrit (usually 45%)
How is viscosity affected in polycynthemia? (increased TPR & BP, slower blood flow)
Viscosity is higher
How is viscosity affected in anaemia? (decreased TPR & BP, HR increased)
Viscosity is lower
Name 3 ways blood returns from systemic circulation to the heart.
- Down Pressure grad. (flow = change in p / R)
- thoracic pump (inhalation increases BF by raising abdo pressure and forcing blood up
- Skeletal muscle pump
According to Bernouilli’s law, how does blood return to the heart?
Also according to Bernouilli’s law, change in pressure and pgh gradients cancel out but kinetic energy of blood allows it to return to heart.
According to Bernouilli’s law, how does ejected blood overcome the pressure to reach the feet?
- ejected blood has a greater KE than at the feet
- has higher potential energy at the heart
Arterial thrombosis tend to be coloured….due to being
Arterial = white due to being platelet rich
Venous thrombosis tend to be coloured….due to being
Venous = red due to being platelet poor
Virchow’s Triad of Thrombosis:
- stasis
- vessel wall injury (smoking, HT, trauma)
- hypercoaguability (hereditary/aquired)
Outline 1ry and 2ndry haemostasis
1ry - platelet adhesion, aggregation and stabilisation of plug with fibrin
2ndry - blood coagulation, dissolution of clot, vessel repair and fibrinolysis
Warfarin and heparin do what
are anti-coagulants
Plasminogen activators, steptokinase do what?
“clot busters” break down clots
Go through what happens in the stages of Atheroma:
- initial lesion
- fatty streak
- ATHEROMA
- FIBROATHEROMA
- COMPLICATED LESION
- initial lesion-mo infiltration, isolated foam cell
- fatty streak-intracellular lipid accumulation
- ATHEROMA-“” + core of extracelluar lipid
- FIBROATHEROMA- ““lipid cores. Fibrotic/calcific layers
- COMP. LESION-surface defect, haematoma, thrombosis
Give 5 risk factors of developing atherosclerosis:
- age
- male (+post-menapause)
- smoking
- hyperlipidemia
- HT, diabetes…
& systemic inflammation
What is involved in the initiation of Atheroscleosis?
- inflammatory mediators activated eg. oxidised LDL
- increased expression of adhesion molecules
- hyper-reactive endothelial layer attracting circulating monocytes
What is involved in plaque formation of Atheroscleosis?
- mo takes up LDL and becomes a foam cell
- releases cytokines activating VSMC
- VSMCs migrate and proliferate in the intima
What is involved in plaque maturation of Atheroscleosis?
- some VSMC that take up LDL and become foam cells undergo apoptosis
- the lipids accumulate into a necrotic core
What is involved in calcification/instability stage of atheroscleosis?
- calcium deposits (from apoptotic foam cells) builds up
- plaque starts to occlude the vessel/break into lumen
What is thrombosis?
- When a plaque ruptures and the lipid/necrotic core is released into the vessel, where it occludes flow
- endothelium disruption exposed TF initiating thrombin formation
Give 3 consequences of Atheroma
- occlusive thrombosis
- thromoembolism
- aneurysm
- peripheral vascular disease
Whats the difference between stable and unstable angina?
Stable-due to permanent flow limitation
Unstable-due to transient thrombosis
Where are baroreceptors found?
How do they sense BP?
Walls of carotid artery and aorta
Sense BP by detecting arterial wall stress
What is the central sympathetic pathway starting from chemoreceptors in response to a low BP?
(Pressor response)
- chemoreceptors excite NTS
- NTS inhibits the CVLM (this is the inhibitory centre)
- CVLM disinhibits the RVLM
- RVLM -> spinal cord, increases sympathetic outflow to heart and blood vessels to increase BP
Why is HR faster on inhalation?
Inhalation switches off parasympathetic vagal nerves
Upon orthostasis, BP drops due but quickly recovers due to…the integration of which 3 changes?
- HR X3
- TPR X3
- Contractility X1.5
so massive increase in O2 uptake by increased pulmonary circulaton
What is postural hypotension?
Upon orthostasis, venous pooling in legs, fall in CVP, decreased SV and CO.
Decreased BP so poorer perfusion to brain
Orthostasis reflex response:
Decreased: baroreceptor stimulation
Switch off inhibitory fibres in the CVLM
RVLM increases symp drive to SAN increases HR
Increased contractility and TPR so BP increases
What 3 things make postural hypotension worse?
- a-adrenergic blockage/drugs that decrease vascular tone
- varicose veins
- reduced circulating blood volume
- increased core temperature-peripheral v.dilation
How does CVS respond to excercise?
-increase symp NS, decreased vagal
-HR x3
-SV x1.5
-(A-V)02 x3
so o2 uptake from the lungs is increased with the greater flow and conc grad. Despite normal BP.
What vessels vasodilate in moderate excercise?
-arterioles in active myocardium and skin
What are mechanoreceptors in skeletal muscles sensitive to?
-K+, H+ and lactate (these increase during excercise)
Name three vasoconstrictors?
Adrenaline
Angiotensin II
ADH
Name a vasodilator?
ANP
How do high levels of K+, adenosine, histamine…cause vasodilation?
They act on the pre-synaptic terminal
And reduce release of NA hence vasodilation as vascular tone is reduced
Where does Adrenaline preferentially act?
At high concentrations where else…
B2 receptors
high concs also a1 receptors
Endothelin 1/ET1 released from endothelium and TXA2 released from aggregating platelets act where to cause what?
Act on VSMC
To cause vasoconstriction
What 3 things stimulate RAAS system?
- low renal blood flow
- sympathetic nerve at B1 receptors
- low plasma NaCl
By which mechanism do a1, AT1, V1, ETA and TXA2 receptors cause vasoconstriction?
via Gaq: PIP2 via PLC –> IL3 and DAG
-increases membrane excitability by increased Na+ and VGCa2+ channels
-increased release of Ca2+ from SR
More calcium leads to more contraction
What causes ANP release?
Where is it released from?
Stretch receptors in the atria detected excess vasoconstriction
Release from atrial specialised myocytes
Give 2 ways ANP acts to reduce BP?
- dilates renal afferent arterioles so more filtration and excretion to decrease blood volume
- at NP receptors on VSMCs it increases the c.GMP pathway causing vasodilation
- decreases RAAS system
How do the parasympathetic nerves e.g. ACh, VIP cause vasodilation?
- they act on endothelium
- cause release of NO
Give 2 situation in which sudomotor fibres may release ACh/VIP (causing vasodilation)
- sympathetic mediated sweating, increased BF makes more sweat to cool down
- blushing
Where can SubP/CGRP released from C fibres act?
What is the purpose of the vasodilation caused?
-on mast cells causing histamine release
-on endothelium and VSM
Both cause skin “flare” increasing WBC for repair
What are the 3 parts of the Lewis Triple Response?
- flare
- local redness
- wheal
How does NO cause vasodilation?
- via eNOS, NO is produced
- NO stimulates GC (guanylate cyclase)
- GMP–>c.GMP–> PKG causing vasodilation
PGI2 is released via COX action, how do they act?
And why is this important in the kidney?
- via prostanoid receptor
- GaS pathway increasing PKA –> vasodilation
- in kidney this maintains BF in arterioles to maintain GFR
3 ways PKG/PKA cause vasodilation in VSMC.
- inhibits MLCK
- Increases SERCA activity
- increases K+ activity–> hyperpolarisation
How does local increases in K+ ions cause VSMC vasodilaton?
- switches on K+ channels
- increases Na/K+ ATPase so more Na+ extruded
- VSMC hyperpolarisation
Why do you get more vasodilation at the heart and skeletal muscle upon sympathetic activity but vasoconstriction at most other sites?
Coronary circulation and skeletal muscle have loads of B2 receptors - Adren acts here, PKA inhibits contraction of smooth muscle (VSMC)
Elsewhere have more a1 receptors leading to sympathetic mediated v.constriction
List 4 compensatory mechanisms in HF
- ventricular dilation
- increased myocardial contractility
- myocardial hypertrophy
- sympathetic stimulation
- RAAS
Explain each of the following disadv.s of prolonged compensatory mechanisms in HF:
- continous symp activation
- increased HR
- increased preload
- increased TPR
- continous symp activation - B-adrenergic downregulation/desensitisation
- increased HR - higher metabolic demand
- increased preload - pressure transmitted to pulmonary vasculature –> pulmonary oedema
- increased TPR - increased afterload –> decreased CO
What is peripheral oedema and raised JVP a sign of?
-Right sided HF
What is pulmonary oedema a sign of?
-Left sided HF
Give 3 symptoms of pulmonary oedema (Left sided HF).
- dysponea
- orthopnea
- paroxysmal nocturnal dysponea
What biomarker is used in the clinical diagnosis of HF?
If elevated what could be requested?
NTproBNP
-request echo/ECG
What is paradoxical cold vasodilation in cutaneous circulation?
After cold induced vasoconstriction, you will eventually get osscilations between this and vasodilation to protect skin damage.
Occurs by paralysis of symp. transmission
What is special functionally about the pulmonary circulation?
- has low vascular resistancs (1/8th vs normal)
- less symp influence
- low pressure aids gas exchange
- HPV
What is HPV-hypoxic pulmonary vasoconstriction?
- prevents blood going to poorly ventilated regions of the lungs as hypoxia increases vasoconstriction on the VSMCs
- optimises V:Q ratio
Where is pulmonary pressure lowest, what does this cause?
Lowest p at the apex so poor perfusion here
Vessels can collapse slightly impairing oxygenation
How does O2 extraction more than double in skeletal muscle during excercise?
(+1 disadv)
- increased flow (+more filtration/oedema)
- capillary recruitment so more SA for exchange and reduced distance for exchange
- steeper conc gradient
Partial occlusion of coronary arteries show what on an ECG?
- NSTEMI
- small ischaemic area doesnt depolarise so ST segment is depressed
Explain how parasympathetic nerves affect HR.
- Ach at M2 receptors (Gai)
- decrease HR
