Case 4 Flashcards
Outline the mechanism of action of GTN spray
An increase in Nitric Oxide activates guanylyl cyclase that raises cGMP that activates PKG that lowers calcium concentration in the Smooth muscle cell
Contractile cells are at rest at what voltage? What channels are in adbundance here?
- membrane potential at -90 mV - several K + channels keeping at -90 mV
What are the membrane potentials of Na, Ca K?
Na - 67 Ca +123 K -92
What happens at contractile cells?
See pictures
What is the refractory period?
Absolute refractory - during depolarisation, unable to stimulate Na + voltage gated channels as they are open or inactive (unable to stimulate unless they are closed) Relative refractory - during repolarisation, able to stimulate Na + channels as some of they have ‘reset’ as they are closed, however a significantly larger stimulus is required as only a few channels are closed
In the ECG, break down what the QRS wave represents?
Q- interventricular septum depolarisation R - ventricular depolarisation going down S - late ventricular depolarisation (small areas of the ventricles activated at a later stage)
What is your U wave?
Prolonged repolarisation of the ventricular repolarisation of perkinjie fibres
What is the PR Interval normally?
0.12 - 0.2 secs (3-5 small sqaures)
What is the normal QRS?
Less that 0.12 sec or 3 small squares
Heart murmur what is it?
- turbulent flow of blood causing swooshing and wooshing
Sinus tachycardia, what is it?
Rate is more than 100 bpm Regular QRS, may or may not get a P wave
What is a cardia arrhythmia?
Disturbance in the initiation and propagation of action potential
What area of the heart is most susceptible to damage?
The AV node
Ectopic beats - what are they?
Cells other than pacemaker cells that initiate an action potential Are irregular and a thump
What is first degree heart block?
When PR interval is MORE THAN 0.12-0.2 seconds Constant PR Interval
What occurs in Second degree heart block?
Not every atrial impulse reaches the ventricles There are two types; Mobitz Type 1 Mobitz Type 2
What is third degree heart block?
AV node fails to transmit any impulses
What leads represent the RIGHT CORONARY ARTERY? What area of the heart is this?
Leads 2, 3 and AVF, Inferior side of heart
What leads represent the Left Anterior Descending artery?
V1- V6 - anterior side of heart
What chest leads represent the circumflex artery?
Leads 1, aVL, V5 and V6 Shows lateral side of heart
Where are the chest leads placed for a 12 lead ECG?
V1 - 4th intercostal space (right) V2- 4th intercostal space (left) V4- 5th intercostal space, left midclavicular line v3- diagonally between v2, v4 V5 a left anterior axillary line V6- left mid axillary line
Mali comes into the clinic to get her ECG done. This patient could have a blockage at her right coronary artery, which leads would you be looking at and why?
Looking at leads 2,3 and AvF As the right coronary artery runs at the inferior portion of heart which is represented by these leads
What is a normal sinus rhythm?
60- 100 bpm Regular QTS P wave always preceding QRS - 1:1
What is the function of endothelial cells?
Endothelial cells are involved in SAHIRS S- secrete Von Willerband Factor AH- Anti-haemostatic agents (nitric oxide, prostacyclin: prevent the aggregation of platelets) I- inflammatory response - histamine and bradykinin for vasodilation R- regulate vascular tone - by NO, EDHF, Endothelin (by sensing shear stress or by receptor agonists) S- semi-permeable
Acetylecholine stimulates the release of what from endothelial cells?
Nitric oxide or endothelium derived relaxing factor
What is the consequence of peroxinitrite production?
Interacts with lipids, DNA and proteins
What are endothelum derived contracting factors?
An example is prostanoids. - when NO is impaired by stretch, ageing, hypertension - they reduce endothelium dependent vasodilations in aged subjects and in hypertensive patients
What forced affect endothelial cells?
1) cyclic strain 2) fluid shear stress
Where might you have disturbed shear stress in blood vessels?
1) areas of high curvatures 2) bifurcations
How is nitric oxide produced by the endothelium?
- Agonist stimulated rise in intracellular Ca2+ and more Ca2+ influx
- eNOS activated and converts L arginine to Nitric Oxide
- Important co factor is BH4 - tetrahydrobiopterin
What is the mechanism of action of NO?
- NO diffuses from tunica intima to tunica media (smooth muscle cells)
- Activates cGMP
- less Ca2+ is mobilised from SR
- less Ca2+ enters by L type Ca2+ channels
- more Ca2+ uptake by SR
- more Ca2+ extruded by calcium ATPase pump
Activates (Ca2+ dependent) K+ channels, hyperpolarises membrane
All leads to vascular relaxation
*
What are endothelium derived hyperpolarising factor?
- bradykinins and Ach
- cause cell to hyperpolarise and thus relax muscle
- in absence of NO
Mechanism of action of EDHF is similar to NO (i.e. increase in Ca2+ ) but what is the difference?
Superoxide broken down to H2O2
H2O2 potentiates EDHF
When does EDHF mechanism take action?
In notes,
- Mainly in small arteries, arterioles
- When bioavailability of NO is compramised by increased superoxide production
What is prinzmetal angina?
Also known as coronary artery spasm, a temporary constriction within the vessel due to partial occlusion of the vessel by lipid build up
Describe the features of this coronary artery histologically
Describe the stages of atherosclerosis
Attatch
What is the role of foam cells in artherogenesis
1- they promote movement of smooth muscle cells from media to intima
2- they promote smooth muscle cell proliferation (synthesises collagen and elastin)
3- they mediate SMCs to secrete calcium which hardens plaque
4- when the foam cells die, they increases chances of rupturing as they release all of their lipid content
What does your first heart sound represent?
AV valves closing - LUB - onset of ventricular systole
What does the second heart sound represent?
Closing of semilunar valve - DUB - onset of ventricular diastole
What does the 4th heart sound represent?
Atrial contraction
What does the 3rd heart sound represent?
Ventricular filling in early diastole
Where might a murmur from regurgitant flow through the aortic valve occur, indicate where on an ECG?
Between the second and third heart sounds
What is the significance of the fibrous skeleton?
1) atrioventricular rings of fibrous tissue
2) anchor valves
3) electrically insulating
What are the four ways pain is brought about during cardiac ischaemia?
*** Pain helps daisy and me protect ***
P - decreased perfusion pressure detected by pressure receptors
h - hypoxia sensitised by chemoreceptors
D - distention of cardial chambers
M,p - pain inducing metabolites such as kinins
What is stable angina?
- ‘tight band like feeling at chest’
- brought on by exertion
- severity and frequency always the same
- pain is relieved by resting, GTN med
What is unstable angina?
1) ‘tight band like feeling in chest’ OF RECENT ONSET
2) Pain comes on less on exertion and more during rest
3) severity and frequency increases
4) a deterioration of stable angina
What are the differences between stable angina, unstable angina and acute coronary syndrome in terms of the coronary lumen characteristics?
Stable Angina - atherosclerotic plaque that is partially occluding the lumen
Unstable angina - atherosclerotic plaque has formed a fibrous cap, partially occluding THROMBUS
STEMI - atherosclerotic plaque with fibrous cap, fully occluding thrombus
What is the leading cause of death worldwide?
Atherothrombosis (MI, stroke, PaD)
By how much does atherthrombosis reduce life expectancy in patients over 60 years old?
8-12 years
How does clopidogrel work?
Clopidogrel and aspirin work synergistically.
1) Aspirin inhibits COX for forming thromboxane A2
2) Thromboxane A2 is unable to activate the membrane receptor.
3) ADP is not released. ADP that that is released from the receptor is competitive inhibited by clopidogrel
4) the fibrinogen receptor is not activated (Gb IIb, Gb IIIa)
Atrial natriuretic peptide is released in response to… Hence it opposes… Thus it…
High blood pressure
Aldosterone
Descreases Na reabsorption in the distal convoluded tubule and collecting duct
