Extra Flashcards
PGI2
Endothelium vasodilator
2 sites in COX
Cyclooxygenate and peroxidase
Vioxx selective for
COX2
Disadvantage of NSAIDs selective for COX
Kidney salt retention, so increase in blood pressure
What do inflammatory mediators do?
Smooth muscle contraction, increased permeability, mucous secretion, platelet activation, stimulation of nerve endings, recruitment and activation of eosinophils
New therapies for treating asthma
Humanised antibodies and soluble receptors to IgE e.g. omalizumab and chemokine,
PGD-12 antagonists (small molecules) inhibits immune cell and mast cell signalling
How big is the AVN?
22mmx10mmx3mm
What is AV refractoriness for?
Prevents excess ventricular contraction
What is the conduction speed of His, purkinje and ventricular myocytes?
His- 1, Purkinje-4, Ventricular myocytes- 1
How does sympathetic nervous system control pacemaker cells?
Noradrenaline, causes increase in pre potential slope so increases firing rate, If channels increase activity by B1 and B2 or decreasing M2 which regulates cAMP
Occurrence of Long QT
1:10000 to 1:15000
Treatment for Long QTs
- B blockers -> class 2 antidysrhthmic drugs e.g. atenolol a B1 (cAMP linked) selective receptor agonist- slows down heart rate so less likely to have a cardiac episode, negative chronotropic and ionotropic effects
Channels cause SQT1,2,3,4,5?
1- Kv11.1a, 2-Kv7.1a, 3-Kir2.1a, 4-Cav1.2a, Cav12B2
Treatment for short QT
Implant defibrillation, research suggests quinidine
What happens in phase 2 of the cardiac cycle?
QRS complex, so contraction of ventricles so rapid rise in pressure, AV valves shut due to increase in ventricular pressure over atria, papillary muscle contraction, S1
Why is S1 sound split?
Because mitral valve closure slightly precedes tricuspid closure
What happens in phase 3 of the cardiac cycle?
Rise in pressure, c wave- bulging of mitral valves back into left atrium
What happens in phase 4 of the cardiac cycle?
Ejection begins when intraventricular pressure exceeds the pressures in the aorta and PA, initial velocity highest, atrial pressure slightly drops due to atrial sucking but then continues to rise due to filling,
What happens in phase 5 of the cardiac cycle?
Valves shut- S2, dicrotic notch where pulmonary and aortic pressures rise, rate of pressure decline in the ventricles is determined by rate of relaxation which is determined by pumping in to SR, no change in vol
What happens in phase 6 of the cardiac cycle?
Intraventricular pressures below atria, so AV valves open allowing blood flow in, most passively (90%) then atrial kick, S3 ventricles fill (normally silent), atria, aortic and pulmonary artery pressures continue to fall in this period
Heart rate in a new born?
70-190
Heart rate in an infant
80-120
Heart rate in children?
70-130
Heart rate in adults
60-100
Heart rate in well trained athletes
40-60
What does Calcium bind to in contraction?
Troponin- causes conformational change in troponin tropomyosin complex
What experiment can measure the length tension relationship?
Papillary muscle length is tethered with thread to force transducer and held in place with a clamp which holds muscle at a set length, an electrical stimulating electrode is used to produce twitch and the force is recorded, muscle is then lengthened and then the twitch is repeated, force is plotted against length on graph to give length tension diagram
What can cause an increase in contractility of the heart?
When more cross bridges form per stimulus (more Calcium per stimulus), quality of the actin/ myosin cross bridges
Why does an increase in frequency increase tension?
More beats means more Calcium influx during plateau via Nav1.2 L-type, depolarisation during plateau of an AP cause Na-Ca exchanger to operate in reverse so calcium enters cell, also increase rate stimulates SERCA2a thereby sequestering Calcium in SR
What is Q1, Q2 and Q3 according to Fick’s principle? What is the equation derived from this?
Q1- rate of delivery, cardiac output x oxygen content in pulmonary artery
Q2- uptake
Q3- rate of removal, cardiac output x oxygen content in pulmonary vein
CO= O2 uptake / [O2]pv - [O2]pa
What are the ways of measuring cardiac output in a patient?
Measure O2 rate by vol and O2 content in expired air, [O2]pa by pulmonary catheter and pv by peripheral arterial blood
Indicator solution- inject tracer into vein/ right ventricle e.g. inocyanine green, measure difference between colour you put in and colour in arterial blood- output is proportional to 1/ [tracer]
Thermodilution- cold saline injected into right atrium, mixes blood, moves to ventricle the pulmonary artery, sensory in artery measures temperature changes, this change with the vol put in is used to measure CO
Ultrasound- changes in ventricle dimensions, stroke vol calculated from this
Parasympathetic nervous control of cardiac output?
Left vagal nerve on AVN and right on SAN, Ach release M receptors which inhibit cAMP so decrease slope (bradycardia), slow conduction through AV node so decrease force per beat
Sympathetic control of cardiac output?
NA to B1 receptors on Nodes and myocardium, increase SA node firing and increases conduction velocity, time for systole and diastole decrease due to increase calcium increasing contractility
What does NA on B1 receptors result in?
B1 receptors are GPCR which stimulates cAMP which stimulates PKA which activates L-type Calcium channels which causes contraction
What humeral factors effect heart rate?
Thyroid hormones
What does tissue fluid formation depend on?
Hydrostatic pressure difference, difference in colloid osmotic pressure, capillary filtration coefficient
What can cause abnormal tissue fluid level?
Haemorrhage (bp reduces so more reabsorption), capillary damage, increase venous BP due to heart failure, pregnancy, venous obstruction causing oedema, inflammatory oedema caused by histamine, hypoproteinaemia, exercise oedema
What are the key targets for control of circulation?
Arteriole resistance, blood storage veins, vascular smooth muscle
What does sympathetic cholinergic control of pre-capillary vessels do?
Vasodilation of skeletal, heart, lung and kidney
What does sympathetic activity of baroreceptors result in?
Increase stroke volume, increase blood pressure, decrease vagal activity to increase cardiac output
What is the pathway after stretch in the carotid sinus?
Signal through the glossopharyngeal nerve, to inhibitory interneurons, thoracic parts of the spinal cord, inhibit contractility
What is the sympathetic pathway from the medulla to the heart?
Cardioaccellatory centre, descending pathway to spinal cord at T1-T4, fibres exit via spinal nerves, enter sympathetic chain (preganglionic and post ganglionic), cardiac nerve, heart, heart rate
What is the parasympathetic pathway from the medulla?
Cardioinhibitory centre, vagus nerve, preganglionic synapses with cardiac plexus, post ganglionic, change heart rate
What is the response to intracranial pressure rise?
Reduced blood flow due to compression on blood vessels, Cushing reflex whereby there is an increase vasoconstriction to force more blood to the brain and bradycardia, therefore there is much less blood flow to brain resulting in high risk of death
What do buffer nerves do?
Increase firing with increase arterial blood pressure, decrease vasoconstrictors and cardioinhbitiion, vasodilation, bradycardia, reduce output and bp
What is the vasalva manouvre?
Forced expiration on a closed glottis, increases thoracic pressure and bp, so reduces venous return which reduces baroreceptors, so vasoconstriction and tachycardia, which increase venous return increased CO and increased bp, when then increases baroreceptor firing, bradycardia and vasodilation and Bp drop giving tachycardia ….
What does activation of chemoreceptors lead to?
Increase BP
What does hypothalamus defence area do?
Vasodilation of skeletal muscle
What is the pharmacological treatment for hypertension?
Diuretics, sympatholytics e.g. a and B blockers, Ca blockers, RAA system and dual approach
What does Clodine do?
Decrease DNS symapthetic output on blood vessels
What do B blockers do?
Reduce heart rate and contractility
Give an example of a broad spectrum calcium channel blocker to treat hypertension?
Miroxidil
Give an example of a selective Calcium channel blocker to treat hypertension?
Manidipine
What may the heart do in 3rd degree heart block?
A node may continue a rhythm to the ventricles OR patient may suffer ventricular stand still leading to syncope or sudden cardiac death
What are symptoms of 3rd degree heart block?
Severe bradycardia with independent atrial and ventricular rates
What is treatment for atrial fibrillation?
Flecanide, B blockers, Amodarone, Dronedarone
What is NHE1 inhibited by?
Low concentrations of amiloride and its analogue EIPA
