Cardiovascular Flashcards
Describe the central neural control of the cardiovascular system reflexes
Cortical influences- emotion
Complex reflex patterns originate in nuclei in the brain- exercise, feeding/satiety, alerting, thermoregulation, reproduction
Simple reflexes originate from the medulla
Reflexes also influence catecholamines, vasopressin, renin I angiotensin system
Describe the autonomic supply of the CVS
Rostral ventrolateral medulla (RVLM)- nucleus, organotopically organised- descending excitatory activity to T1➡ L1-2- increases HR via beta1 receptors, stimulates adrenaline secretion, and vasoconstriction
Vagus- decreases HR via muscarinic receptors
Describe the baroreceptor reflex pathway
Decrease ABP, decrease baroreceptors firing
Input from CN 9&10 to nucleus tractus solitarius
➡ inhibit nucleus ambiguus less
➡ inhibit RVLM less
Increase HR and vasoconstriction
➡ inhibit SON and PVN➡ inhibit pituitary less➡ ADH release
What are the functions of the baroreceptor reflex
Continuously buffers changes in ABP
Increase during exercise, coughs, sneezes
Decrease during standing up, dehydration or haemorrhage , digestion, thermoregulation in high temperature
Describe the atrial stretch receptor reflex
Decrease blood volume- decrease afferent activity to NTS➡ paraventricular nuclei➡ increase sympathetic activity to kidney via a pathway that by bypasses RVLM and via renal nerves from the RVLM➡ increases renal vasoconstriction➡ decrease GFR➡ renin➡ angiotensin➡ ADH➡ increase blood volume
Describe the 2 main mechanisms that regulate the respiratory influence on the heart
Central nervous mechanisms- central insoiratory drive (CID) excites the phrenic nerve and inhibits the nucleus ambiguus decreasing vagus influence in the heart increasing HR
Reflex from pulmonary stretch receptors- inspiration➡ pulmonary stretch receptors➡ NTS➡ inhibit nucleus ambiguus➡ decrease vagus➡ increase HR
Briefly describe the two reflexes from peripheral chemoreceptor stimulation?
From hypoxia
When respiration cannot increase- primary cardiovascular reflex response to chemoreceptor stimulation dominates to decrease HR, vasoconstriction (except brain) to conserve oxygen
When respiration can increase- effects of increase respiration increases HR
When might someone get systemic hypoxia when respiration cannot increase?
Under muscle relaxant- ventilated at a constant rate and depth
High spinal transection
Long dive underwater
Fetus in utero
Severe respiratory disease
Superimposed upon local effects of hypoxia- decrease HR and contractility, cerebral, muscle and coronary vasodilation, pulmonary basic instruction (pulmonary oedema, right ventricular failure, systemic oedema)
When might someone get systemic hypoxia when respiration can increase?
Hypoxia atmosphere
High altitude
Less severe respiratory disease
Increase in respiration and heart rate plus vasocontriction in GIT, kidney, helps to restore PaO2 so systemic tisdures do not become as hypoxic and pulmonary vasoconstriction is less severe
Describe the diving reflex
Reflex evoked by trigeminal receptors
Cold water on face/nose
Inhibition of central inspiratory neurones➡ expiratory apnoea and decrease HR, vasoconstriction
O2 conserving
Clinically receptors stimulated by sinus washing, irritant vapours, intubation, lumps of food in the pharynx
Describe the changes in oxygen consumption in dynamic exercise
Requires an increase in ventilation and cardiac input
O2 consumption is graded with work load up to a maximum the anaerobic threshold
Recovery after exercise to repay the oxygen debt
Describe the change in cardiac output with dynamic exercise
Heart rate increases in a graded manner with graded dynamic exercise up to a max ~220 beats/min minus age
Increase SV is dependent on contractility and venous return which is greater when supine with the skeletal muscle pump and respiratory pump
Greater proportion of output goes to skeletal and cardiac muscles at the expense of the viscera- muscle contraction interferes with vasodilation
Describe the local effects of exercising muscles on the cardiovascular and respiratory system
Exercise hyperaemia- local vasodilation
K, P, adenosine released by muscle into interstitial space
Graded with exercise intensity
PGI2, NO from endothelium
Causes relaxation of vascular smooth muscle
Counteracted by mechanical influence of contracting muscles
What is the exercise reflex?
K, P and adenosine released stimulate metaboreceptors
Joint receptors are also stimulated in dynamic exercise
Reflex tachycardia
Metaboreceptors➡️ medulla ➡️subthalamic locomotor region (hypothalamus) the exercise integrating area
Increase motor activity to diaphragm and intercostal muscles to increase respiration, increase sympathetic and decrease parasympathetic to the heart
Increase sympathetic noradrenergic activity- Reflex vasoconstriction in GIT, kidney, skin and all skeletal muscles
Via connections with central respiratory neurones, cardiac vagal motor neurones and RVLM to sympathetic pre-ganglionic neurones
Describe the central command involved in dynamic exercise
Subthalamic locomotor region (SLR) in the hypothalamus
Exercise integrating area received inputs from the cortex
Result in increase respiration, HR CO and vasoconstriction in GIT
Also increase set point of baroreceptors
Describe static exercise
Metabolites get trapped in the contracted muscle and cause greater stimulation of metaboreceptors
Exercise reflex is greater of a given work load than during dynamic exercise
Large increase in ABP
Exercise hyperaemia occurs after static exercise
Time limited- fatigue occurs relatively quickly
Oxygen delivery is limited
Carries cardiovascular risk
Describe hypoxia due to altitude in humans
Tolerant until 60mmHg or 8kPa of oxygen in blood- when desaturation starts
Symptoms start to appear when blood is less than 90% saturated eg. Loss of visual acuity then postural stability iand recall and reaction time decreases under 80%
What are the acute responses to altitude?
Low PO2 stimulates peripheral chemoreceptors leading to ventilation (which is opposed to varying degrees by hypoxia depressing respiratory centres
Hyperventilation causes a fall in PaCO2➡ hypocapnia and rise ikn pH (respiratory alkalosis)➡ inhibition of peripheral and central chemoreceptors➡ slight fall in total ventilation- reduces the response too hypoxia
Fall in CO2 also means that oxygen delivery to tissues is not as efficient as Hb affinity for ocyhgen increases
Loss of CO2 can also cause Cheyne-Stokes respiration while asleep
However hyper ventilation is necessary to reduce the risk of severe hypoxia by decreasing the space taken up by CO2 in the alveoli and keeps the partial pressure of the gases as high as possible for effective diffusion
Describe the cardiovascular response to altitude
Tachycardia caused by hyperventilation by action on the nucleus ambiguus
Reduce peripheral resistance raises tissue perfusion
Cerebral blood flow- vasoconstriction due to the altitude induced hyperventilation- very response I’ve to CO2 but not O2- severe hypoxia leads to vssodilation
Pulmonary circulation- hypoxic vasoconstriction helps V/Q- promotes blood flow to the best alveoli
What is mountain sickness?
Headache above 2500m plus: dizziness, irritability, vomiting, nausea, sweating, breathlessness, insomnia, fatigue
Thought to be caused by cerebral oedema- hypoxia dilation increases cerebral capillary filtration pressure and hypoxia induced increased permeability
Pulmonary oedema- uneven hypoxia vasoconstriction of pulmonary vessels leading to pulmonary hypertension, increased capillary permeability- protein leakage
Treated by supplementary oxygen and reducing altitude
What are chronic responses to high altitude?
Adaptive and alcclimatization
Body compensates for low PO2 and improve O2 delivery to tissues
Hyperventilation increases again as the altered pH is restored (HCO3 moves away from the CSF to resdtore cerebral pH and metabolic compensation for respiratory alkalosis decreased HCO3 reabsorption and H secretion) which leads to 2,3 DPG production to decrease O2 binding affinity, and peripheral chemoreceptor sensitivity increases
Also the O2 carrying capacity in blood is increased by increased EPO, increased RBC count and Hb conc
More pulmonary capillaries open
HR increases but SV decreases so CO is restored
Angiogenesis, increased cytochrome oxidase, increased myoglobin content in sketal muscle in tissues
Describe calcium channel blockers as vasodilators
Stop influx of calcium to the smooth muscle cell of the vessel and initiating contraction
Dihydropyridine (DHPs) eg. Nifidipine, nimodipine
L-type channel blockers
Used in angina for coronary vessel walls and systemic vessels (more constriction in veins)
Peripheral vascular disease- Raynaud’s sydrome- extreme basic instruction in extremities
May have use for improved cerebral function after a stroke or in dementia
Side effects- flushing and decreased GIT activity
Describe K channel blockers as vasodilators
Open K channels to allow K efflux and causing the hyperpolarisation of the cell
Eg. Minoxidil, cromakalim
Work by ATP-modukated K channels (K(ATP))
Primarily arterial effects to reduce total peripheral resistance
Used in severe hypertension only as there are more side effects- headache/flushing, tachycardia, oedema
Describe organic nitrates as vasodilators
Eg glyceryl trinitrate (GTN)
Work by releasing NO to upregulate guanylyl cyclase
Used in angina, coronary vessels and systemic circulation (more constriction in arterioles)
Side effects- excess vasodilation- hypotension, refelkx tachycardia, headache
Administered sublingually or transdermally for prophylaxis
Other egs. Isosorbide mono/dinitrate
Amyl nitrate (Poppers)- tolerance
Sodium nitroprusside- NO release to increase cA/GMP- used in hypertensive emergencies
Describe PDE inhibitors as vasodilators
Phospohodiesterases degrade cGMP
PDE type 5- sildenafil (Viagra) used in impotence- erection
What are the causes of heart failure?
2\3 have systolic failure
2/3 of those have impaired contractility due to myocardial infarction, transient myocardial ischaemia, chronic volume overload- valve regurgitation, atrial fibrillation
1/3 have increased after load- pressure after load, aortic stenosis, uncontrolled hypertension
Systolic dysfunction leads to left heart failure which generally leads to right heart failure (backward failure)
If the ejection is less than 50% indicative oif heart failure- dilated ventricle, increased EDV, depressed contractility
What are the signs and symptoms of congestive heart failure?
Coughing Tiredness Shortness of breath Pulmonary oedema Heart pumping becomes weaker Pleural effusion Ascites Oedema in ankles and legs
What is the new York heart association classification of heart failure and its significance?
- No limitation of physical activity
- Slight limitation of activity. Dyspnoea and fatigue with moderate physical activity
- Marked limitation of activity. Dyspnoea with minimal activity
- Severe limitation of activity. Symptoms are present even at rest
At class 1&2 SV can still be normalised at rest by an increase in EDV
Class 3&4 the starlings relationship is approaching horizontal
What is the importance of the baroreceptor reflex in heart failure?
Keepos ABP around normal
CO decrease➡ decrease Baro activity➡
Increase sympathetics to heart and blood vessels to increase HR, contractility and venous and arterial constriction
Increase ADH to increase blood volume
Sympathetics to the kidney too increase renin-angiotensin ➡ angiotensin 2 and aldosterone increase Na retention
Decompensation- worsens primary condition- more volume overload
Needs vasodilators, diuretics, beta1 blockers
Sensitivity of baroreceptors decreases and so ABP goes uncorrected
What is ANP and BNP?
Atrial natriuretic peptide
Released in response to increased atrial stretch and ventricular volume overload BNP is only produced in heart failure
Act on the NPR-A receptor to cause vasodilation
Also result in increase diuresis and naturesis to decrease blood volume- counteracts Angiotensin 2 and its effects on aldosterone and ADH secretio
What are the decompensatory outcomes of heart failure?
Increase sympathetics to heart- ventricular hypertrophy, decrease sensitivity to noradrenaline and adrenaline
Loss of vagal effects
Increase angiotensin 2- increase cytokines, ROS generation, adverse remodelling of heart
Chronic sympathetic activity due to ROIS and A2 on NTS, RVLM and PVH
Increase in arginine vasopressin despite volume overload- hyponatraemia- central neural oedema
Exercise intolerance
Endothelial dysfunction
Explain exercise intolerance in CHF patients
Lungs- increase vascular resistance, lung stiffness, oedema, decrease O2 diffusion
Heart and blood- smaller CO, smaller systemic O2 delivery
Skeletal muscle- smaller increase in blood flow, less O2 supply, increase metabolite accumulation, exaggerated music!me reflex
Exercise rehabilitation helpos to prevent downward spiral
Describe platelet adhesion
vVF acts as a bridge between collagen and GP1b/IX/V
Integrin alpha2-beta1 and GPVI binds to collagen
Describe the amplification mechanisms for platelet function
ADP, TXA2, 5HT released from platelet dense granules feeds back to act in platelets to activate them further by increasing intracellular Ca which increases secretion
Thromboxane made from phospholipids (PLA2, Ca)➡️ arachadonic acid (COX-1)➡️ cyclic endoperoxidases (Tx-synthase)➡️ thromboxane A2
Describe platelet secretion
ADP, Ca, 5HT from dense granules
Fibrinogen, beta-Thromboglobulin, VWF, FV, PDGF, multimerin
ADP signalling- acts in P2Y12 and P2Y1 to activate GI, G12 and Gq down regulates AC to increase ADP and up-regulates PLC which causes aggregation and shape change
Describe platelet aggregation
Integrin alphaIIb-beta3 on platelet surface membranes bridged by fibrin and fibrinogen
Scramblase catalyses the movements of phosphotidylserine from the cytosolic leaflet to the outer leaflet of the platelet cell surface membrane
Lost some drugs that affect amplification mechanisms
Aspirin and NSAIDS- block COX1 in thromboxane production
List some drugs that interfere with ADP signalling?
Clopidogrel Prasugrel- pro drugs Ticagrelor- direct antagonist Cangrelor Interfer with the P2Y12 receptor- antagonists
List some drugs involved with platelet aggregation
Abciximab
Eptifibatide
Tirofiban
Affect integrin alphaIIb-beta3, fibrinogen/fibrin/VWF binding- antagonists
Describe the ideal anticoagulant
Oral
A wide therapeutic index
Predictable pharmacokinetics and dynamics
Rapid onset
An antidote
Minimal non-anticoagulant side effects
Minimal interactions with other drugs and food
What are the most basic oral anticoagulants?
Heparin inactivated thrombin and F10a, short half life
Vitamin K antagonists (VKA) (vit K is needed to perform essential post-translational modification of key-clotting factors F2,7,9,10)
What are ODIs anticoagulants?
Oral direct inhibitors
Direct F10a inhibition- rivaroxaban, apixaban, edoxaban
Direct thrombin inhibition- dabigatran
