Ageing Heart Flashcards
How does Calcium transients contribute to raise in mmHg?
allows for ca2+ influx
describe the journey of calcium within cardiac myocytes
- Ca enters the sarcolemma
- Ca binds to sarcoplasmic reticulum and becomes an inorganic ion
- the inorganic ca binds to troponin c on the myofilament
- the molecule becomes SERCa2+ phospholamban
which has faster Ca2+ accumulation, adult cells or SC?
adult cells
what needs to be produced in order for the ca2+ to be transported?
production of ATP form mitochondrion form lactate, fat, glucose
what does a cardiac mri show?
structure and function of the heart
how does a cardiac mri work? (three things)
- using 31P to calculate PCr/ ATP ratios
- high resolution
- non invasive MR tagging
what does MR tagging show within a cardiac mri? (3 things)
- left ventricular mass
- blood pool volume
- ejection fraction
how do you calculate cardiac output?
CO= stroke volume x HR
How do you calculate ejection fraction?
EJ = (stroke vol/ end diastolic vol) x 100
how do you work out stroke volume?
difference between end-diastolic and end-systolic volume
at what time is the lowest blood pool volume?
400ms
what happens with CO with age?
it decreases
what happens to systolic bp with age ?
it increases
what happens to systolic bp with age ?
it increases
what happens to diastolic bp with age?
it decreases
what happens to the heart during heart failure
there is a reduction in the hearts ability to relax and contract
how many people in the UK have HF?
900,000
what percentage does HF relate to A/E admissions in the UK?
5%
what expenditure does HF contribute to?
2%
what are 4 risk factors for HF - reduced ejection fraction?
MI, alcohol, chemo, hypertension
how fast do symptoms of HF- rEF occur?
fast
what 3 things are risk factors for HF- pEF?
- hypertension
- diabetes
- obesity
how fast do symptoms of HF- pEF present?
gradual onset
what do pEF and rEF have in common?
similar symptoms which leads to terminal decline and death
in rEF, what occurs within neurohormonal activation?
- activation of sympathetic NS
- initial maintenance of arterial bp due to fall in CO
- leads to water retention, progressive LV re-modelling
what is the function of renin- angiotensin- aldosterone system?
regulate blood pressure and fluids
what do ACEi do and what does it treat?
an inhibitor of renin to angiotensin II
treats hypertension and reduces HF mortality
what is the function of ARB?
prevents angiotensin II binding to its receptor
what do beta blockers do?
produce negative chronotropic and inotropic effects
what are chronotropic effects?
the increase of heart rate
what are inotropic effects?
the increase of contractability
what are the adverse affects of using drugs to control RAAS system?
mainly only reduce bp - not actually treating HF
highly complex - patient needs to be in full understanding
electrolytes and renal function needs close monitoring
specialist care required - mdt
what causes HF- pEF?
rise in hypertension
atrial fibrillation
diabetes
ischaemic heart disease
what is the most common type of HF?
left ventricular systolic dsyfunction
what is the basis of HF- REF?
unpaired contractions
what is the basis of HF- PEF?
muscle thickening
what 3 drug classes are the most optimal way to treat HF?
- ACE inhib
- beta blockers
- mineralocorticoid antagonists eg aldosterone
name three ACE inhib
- ramipril
- lisonopril
- enalpril
what are the side effects of using ACE inhib?
dry cough, hyperkalaemia, renal impairments
where is renin release from?
renal juxtaglomerular apparatus
what conditions leads to the release of renin?
- reduced na delivery to dct
- reduced perfusion pressure in kidney
- sympathetic stimulation of JGA via B1 adrenoreceptors
where is angiotensin I produced?
liver
where is angiotensin II produced?
lungs
what affects do angiotensin II have on the cardio system
increase total peripheral resistance, which increases blood pressure
increases cardiac output
what other systemic effects does angiotensin II have?
increases ADH secretion
more noradrenaline
increases na reabsorption within dct
what does aldosterone do within the RAAS system?
increases na channel expression
increases na/k/ ATPase activity
what hormone does angiotensin II stimulate the release of?
aldosterone
according to PHE, 2019, how many global deaths are due to poor cardiovascular health?
17.9 million which is approximately 31%
of the 17.9 million CVD deaths annually, how many are CHD?
9.43 million
out of 17.9 million CVD global deaths how many are due to stroke?
5.78 million
out of 17.9 million how many CVD deaths are from COPD?
3.04 million
according to the BHF, 2022, how many people are living with heart/ circulatory diseases within the UK
7.6 million
in the UK (BHF, 2022) how often does someone die from heart/ circ diseases?
every 3 mins
in the UK (BHF, 2022) how often is someone admitted due to a stroke?
every 5 mins
what percentage of the UK pop are born with CHD?
1-2 %
what is the UK survival rate following a heart attack?
7/10
what factors are responsible for CVD?
environment, genetics and ageing
name some examples of treatable RF caused by the environment that contributes to the pathogenesis of heart diseases
- smoking
- stress
- diet
- exercise
what medical conditions increases the risk of heart disease?
metabolic syndrome, central obesity, hypertension, high triglycerides, low density cholesterol, insulin resistance
what is metabolic syndrome
cluster conditions that increases the risk of heart disease
what are the pathological mechanisms causing heart disease?
- dysregulation of the cell cycle
- oxidative stress
- abnormal ca signalling
- vascular inflammation
how does dysregulation of the cell cycle contribute to heart disease?
more senescent cells and no more division to create healthy cells
how does oxidative stress contribute to heart disease?
the build up of reactive oxygen species and nitrogen species
how does abnormal ca signalling contribute to heart disease?
linked to Ca inorganic/ K+ signalling
more hyperpolarisation which causes more small resistance arteries
how does vascular inflammation contribute to heart disease
more endothelial dysfunction, leads to more arterial remodelling
what is hyperuricemia and who is affected the most?
increased uric levels, highest in older women.
7mg/ dL
what does the amount of SC show?
can be an independent predictor of mortality
contributes to arterial stiffness
what happens to endothelial cells when they age?
become flatter/ enlarged with polypoid nucleus
what is atherosclerosis?
hardening and thickening of the walls of arteries
what is the aetiology of atherosclerosis?
caused by the buildup of plaque within inner lining of arteries. plaque made up of fatty substances, cholesterol, cellular waste products, ca2+, fibrin
what is the aetiology of atherosclerosis?
- fatty deposits on the inner lining
- calcification of walls
- thickening of the muscular wall
is atherosclerosis an inflam disease?
yes - categorised by the increased monocytes, macrophages, dendritic cells
how does atherosclerosis result in a thrombus formation?
build up of lipid core - fibrous cap produced - rupturing causes platelets and then a thrombus is formed
what happens when endothelial and platelets activate?
adhesions, differentiation to macrophages, proteolysis and chemotaxis
how would you diagnose atherosclerosis?
- symptoms - angina pectoris, dsypnea
- ecg - can show heart attack
- echo - shows abnormal wall motion
- stress test - shows abnormal chamges in bp/ hr change in rhythm
- coronary CT imaging
- coronary angiography - maps vessels - identifies coronary stenosis
what is the issue with atherosclerosis and treatment?
can only treat the symptoms
how do you treat a stroke?
thrombolysis, embolectomy, medication to reduce blood pressure, break down blood clots
how do you treat coronary heart syndrome?
if it progresses to acute MI - stent or bypass
how do you treat aortic syndrome?
stent
how do you treat peripheral artery occulsion?
anticoagulation, thrombolysis, embolectomy, percutaneous revascularisation, surgery
how does AB1 -40 link to CVD?
amyloid- beta hypothesis in Alzheimer’s increases CVD risk
what is veriguat?
a novel soluble granulate cyclase stimulator which enhances guanosine monophosphate pathway
how is GMP linked to the heart?
GMP is a secondary messenger within nitric oxide pathway and NO is a vasodilator
2020 ref, what happens to those with HF-rEF if they require hospitalisation within 1 yr of urgent treatment?
poor prognosis
2020 ref, what condition is veriguat given for?
used for those with reduced EF and gives a better prognosis than the placebo in the study
2020 ref, what are the side effects of veriguat?
more syncope, dsypnea - due to lower haemoglobin levels
what is amyloid beta within cerebrovascular disease?
cerebral amyloid angiopathy
what is the main amyloid beta peptide within the vascular system?
AB1-40
where is AB1-40 found in cardiac system?
tunica media, smooth muscle cells and adventica, produced in platelets, plaque invading macrophages, endothelial cells
what does high density lipoprotein and apolipoprteoiin E clear?
AB1-42 not AB1-40
what does AB1-40 do to the heart? 2020 ref
more vasoconstriction, more ROS, telomere shortening - promotes vascular ageing
stimulates platelets activation and adhesions
predicts coronary artery disease mortality risk
atherothrombosis
what NT is responsible for increasing heart rate?
acetylcholine
what is meant by venous return drops?
drop in cardiac output and drop in mean arterial blood pressure
what happens to baroreceptors when bp drops?
there is less tension applied to them and they are less stretched, so there is less neuronal firing to the medulla
where is the vagal nerve that detects the increase in ventricular contractions?
it is the main PNS nerve, the mechanoreceptors in the aortic arch relay BP levels via vagal nerve fibres
once the medulla has received the signal of drop in blood pressure causing vigorous ventricular contractions, what does the medulla do to increase BP and decrease HR to normal?
nucleus of solitary tract then activates neurones in the ventrolateral medulla that controls SNS that innervates neurones to increase HR
in atherosclerosis, how does tissue hypoperfusion occur?
hypoperfusion is the the shock to tissues which is caused by narrowing of lumen of arteries, which leads to ischamia
what is ischaemia?
insufficient blood supply
in atherosclerosis, what happens if the plaques rupture?
acute thrombosis, acute artery occlusion, tissue death, organ failure and then death
