Cardiovascular Flashcards
heart failure impairs which part of the cardiac cycle
Isovolumetric relaxation phase
Same phase where coronary arteries supply the myocardium
2 determinants of cardiac stroke volume?
preload and afterload
preload is determined by which two things?
- starlings law of the heart
2. cardiac contractibility
high blood pressure increases____of heart
afterload
what is Laplaces law?
As radius of heart increases for example with dilated cardiomyopathies, decrease in pressure generated and therefore the contractility of the heart falls
P= 2T/R P= 2SW/r
describe:
1 finding in aortic stenosis
1 possible side effect
finding = systolic murmur
side effect = left ventricular hypertrophy (increased afterload in LV)
describe:
1 finding in mitral stenosis
1 possible side effect
finding = diastolic murmur
side effect = atrial fibrillation (increased pressure in LA)
describe:
1 finding in mitral regurgitation
1 possible side effect
systolic murmur
decreased cardiac output -> congestive heart failure
describe:
1 finding in aortic regurgitation
1 possible side effect
diastolic murmur
left ventricular dilation, heart failure
describe the pathophysiology of dilated cardiomyopathy
Dilated and thin-walled heart chambers with reduced contractility
- VOLUME overload - eccentric hypertrophy
- reduced contractility
- reduced systolic function
- reduced ejection fraction
most common causes of dilated cardiomyopathy?
alcohol, chemotherapy, pregnancy, genetic, idiopathic, viral infections, tachycardia-related cardiomyopathy
also thyroid disease, muscular dystrophy
What genes have been implicated in the diagnosis of dilated cardiomyopathy
Mutations in genes encoding cardiac cytoskeleton proteins. E.g. titin, lamin
treatments for dilated cardiomyopathy?
ACE inhibitors beta-blockers anticoagulants for atrial fibrillation mineralocorticoid receptor antagonists diuretics for fluid overload ICD
signs of dilated cardiomyopathy
- GLOBAL HYPOKENESIS on echocardiogram
- edema
- chest pain
- reduced exercise capacity
- fatigue
- ascites
- complications like abnormal heart rhythms
- heart murmurs
risks of dilated cardiomyopathy?
- heart failure
- cardiac arrhythmias
- sudden cardiac death due to ventricular arrhythmia
causes of hypertrophic cardiomyopathy?
chronic PRESSURE overload - e.g due to aortic stenosis or Hypertension
describe the pathophysiology of Arrhythmogenic right ventricular cardiomyopathy.
what are the possible side effects?
- heart muscle of RV replaced by fatty and or fibrous tissue
- right ventricle dilated
- ventricular tachycardia and sudden death
treatment for structural heart diseases?
aortic valve replacement
what is cardiogenic shock?
Impairment in cardiac systolic function, resulting in reduced cardiac output causing end organ dysfunction -
findings in cardiogenic shock?
echocardiogram shows ventricles not pumping
cause of cardiogenic shock?
- mostly MI - STEMI mostly
how do you treat cardiogenic shock?
PCI/CABG and inotropes to increase stroke volume
persistent shock -> Impella, VA-ECMO.
Angiosarcoma is …..?
malignancy of vascular endothelial cells
of skin, heart, liver etc
Myxoma is …..?
tumour of connective tissue of heart
state 3 reasons why cardiac cancers are rare
Low exposure to carcinogens
High turnover rate of myocytes
Strong selective advantage against things that can compromise function
stroke volume equation?
SV = EDV - ESV
cardiac output equation?
CO = SV x HR
convert SV from ml to L
ejection fraction equation?
ejection fraction = (SV/EDV) x 100
Mean arterial pressure equation?
MAP = DBP + 1/3PP PP = SBP - DBP
what is infective endocarditis?
infection caused by bacteria that enters blood stream and affects heart lining, a heart valve or a blood vessel
what are the dukes criteria for infective endocarditis?
major criteria:
- May be a new regurgitation murmur
- Blood cultures may isolate a microorganism
- Echocardiogram can show vegetation, abscess, valve perforation and/or new dehiscence of prosthetic valve.
- Blood tests show anemia and raised markers of infection
- coxiella burnetti infection
minor criteria:
- FEVER >38
- predisposing heart condition or IV drug use
- emboli to organs, brain
- immunologic - glomerulonephritis, oslers nodes, roth spots
- must have a certain combination to ascertain IE
- blood tests may also show aneamia or raised markers of infection, night sweats
what features of decompensation would you look for in infective endocarditis?
Cardiac decompensation - swelling of legs and abdomen, fatigue, frequent coughing, shortness of breath
Clinical signs like raised JVP, lung crackles, oedema
Vascular and embolic phenomena - stroke, janeway lesions, splinter/conjunctival haemorrhages
Immunological phenomena - osler nodes, roth spots
which part of the heart does infective endocarditis affect?
Endocardium, especially the valves of the heart
Aortic valve is most frequently affected (aortic > mitral > right sided valves)
describe the mechanism of ACE inhibitors
Inhibit the angiotensin converting enzyme. Prevent the conversion of angiotensin I to angiotensin II by ACE.
preventing arteriolar vasoconstriction, pituitary ADH secretion, sympathetic activity, adrenal adolsterone secretion and resulting salt and water retention.
Which drug classes are used to treat hypertension?
- ACE inhibitors
- Calcium Channel Blockers
- Thiazide or Thiazide like diuretics
- ARBs
Name ACE inhibitors.
“PRIL” drugs
Ramipril, lisinopril, Perindopril
what are some side effects of ACE inhibitors?
cough, hyperkalemia, foetal injury, renal failure (in patients with renal artery stenosis), Angioedema
why are ACE inhibitors associated with cough whereas ARBS are not?
Increase of bradykinin as ACE enzyme can not break it down
Why might ACE inhibitors and ARBs have a negative effect on eGFR?
Angiotensin II is the major determinant of efferent vasoconstriction.
Ang II effect helps maintain GFR when renal perfusion is low e.g. bilateral renal artery stenosis, volume depletion, and elderly patients with CHF
Blocking the effect of Ang II with ACE and ARBS can cause acute renal failure (GFR decreases because glomerular capillary pressure falls as a result of efferent arteriole vasodilation)
Ramipril like most ace inhibitors is a pro drug where lisinopril is not. what does this mean?
Pro-drug - inactive before metabolism
Active drug - takes the effect directly
what is the mechanism of ARBs?
non-competitive antagonists at AT1 receptor on kidneys and vasculature
some side effects of ARBs
hyperkalemia, foetal injury, renal failure (in patients with renal artery stenosis)
Name ARBs
“Sartan” drugs
Losartan, Irbesartan, Candesartan
what is the mechanism of calcium channel blockers?
Block L-type calcium channels – predominantly on vascular smooth muscle. This results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation.
vasodilation - > decreased peripheral resistance
Some block the channels on cardiac muscle and decrease contractility -> decreased CO
Name some calcium channel blockers
“PINE” drugs
amlodipine
felodipine
side effects of CCBs?
peripheral eodema, flushing headaches, palpitations
What is the key difference in treating patients with amlodipine vs felodipine?
Felodipine has a higher plasma clearance rate, a shorter elimination half life, and a shorter time to peak in plasma levels than amlodipine
- thus felodipine is faster acting
- but amlodipine will still be effective in morning after sleep
which CCB causes reflex tachycardia ( vasodilation and drop in bp causes increase in SNS activity)?
Felodipine
when might you avoid ACE inhibitors and ARBs?
before surgery as hyperkalemia may cause problems
what is the mechanism of thiazide like diuretics?
They block the Na+, Cl- co-transporter in the early DCT.
name some thiazide like diuretics.
thiaziade, indapamide (thaizide-like)
what are some side effects of thiazide like diuretics?
Hypokalemia, Hyponatremia,Metabolic alkalosis (increased hydrogen ion excretion), Hypercalcemia, Hyperglycemia (hyperpolarised pancreatic beta cells), Hyperuricemia.
describe the electrode placement for Leads 1-3
Lead 1 = right arm to L eft arm
Lead 2 = right arm to L eft L eg
Lead 3 = L eft arm to L eft L eg
describe the electrode placement for V1-6
V1 = right sternal border-4th intercostal space V2 = left sternal border 4th intercostal space V4 = left midclavicular line 5th space V5 = at level of V4, anterior axillary line V6 = at level of V4, mid-axillary line V3 = halfway between V2 and 4
label an ECG trace with the leads, their corresponding views of the heart and corresponding arteries (arteries occluded during ST elevation of each lead)
refer to notes
label an ECG trace with the leads, their corresponding views of the heart and corresponding arteries (arteries occluded during MI shown through ST elevation of lead)
refer to notes
1 small vertical square on an ecg represents?
1 small vertical square in ECG = 0.1 mV. 1mV (2 large squares) = 10mm. So 1 small square = 1mm
1 small horizontal square on an ecg represents?
0.04 seconds
a normal cardiac axis range is between?
-30 to + 90
to calculate the cardiac axis what do you need?
two leads that are perpendicular/90 degrees apart
e.g. lead II and AVL
what happens in sinus arhhythmia?
R-R interval varies with breathing cycle
what happens in sinus bradycardia
even R-R but slow
- can be healthy, caused by medicaition or vagal stimulation
what happens in sinus bradycardia
even R-R/ regular rate but slow
- can be healthy, caused by medication or vagal stimulation
what happens in sinus tachycardia
even R-R/ rate regular but fast
what happens in atrial flutter?
regular saw tooth pattern in baseline in leads II, III, aVF
what happens in 1st degree heart block?
prolonged PR interval. normal is 0.12-0.2s
1:1 ratio of p waves to QRS complex
a progressive disease of ageing
what happens in second degree heart block type 1?
gradual prolongation of PR interval until a beat is skipped (QRS missed out)
caused by diseased AV node
what happens in second degree heart block type 2?
no PR elongation, however missing QRS complex. can be in a ratio e.g. 2:1 or random
what happens in 3rd degree/ complete heart block?
p waves are not spaced at the same rhythm as R-R intervals. Constant P-P and R-R intervals
P waves can also be hidden within bigger vectors and not show up on ECG
Atria and ventricles beat asynchronously. Atrial is faster. Can be missing QRS.
what happens in ventricular tachycardia?
- rate is fast and regular - 100-200bpm
- risk of deteriorating into fibrillation
- hidden p waves
- shockable rhythm
what happens in ventricular fibrillation?
- rate is fast and irregular- 250 bpm and above
- shockable rhythm
- VF = CARDIAC ARREST
what causes ST elevation?
infarction - ST segment is elevated >2mm
what causes ST depression?
myocardial ischeamia.
ST segment depressed > 2mm
what is a normal PR interval?
0.12 - 0.20 seconds
left and right bundle branch blocks result in?
wide QRS complex
treatment for a myocardial infarction?
stent insertion, bypass
how do you calculate heart rate from ECG strip
1/R-R = Beats per second
x 60 = per minute
how do you calculate pH
-log10[H+]
what is Fi02?
Inspired oxygen - 0.21= 21% oxygen = room air
Percentage of respiratory acid to metabolic acid in body?
99% respiratory
how does your body compensate for changes in pH?
Changes in ventilation rate
Kidneys change in HCO3- and H+ secretion and excretion
how do you interpret an arterial blood gas? give tips
high pH= alkalosis and vice versa
base excess is neutral =uncompensated respiratory
PaCo2 is neutral = uncompensated metabolic
mixed issue= base excess and PaCO2 are going in opposite directions.
Partially compensated issue - PaCO2 and base excess are going in the same direction. Ph has not normalised
Fully compensated - pH is normal, can’t determine exact issue
hyperventilation causes____?
respiratory alkalosis
hypoventilation causes___?
respiratory acidosis
diarrhoea causes ___?
metabolic acidosis
vomiting causes____?
metabolic alkalosis. (loss of gastric acid secretions/H+)
What is the basic structure of blood vessels?
Tunica intima (endothelium) - inner layer Tunica media (smooth muscle cells) Tunica adventitia (vasa vasorum, nerves) - outer layer
Describe how capillary and venule structure differ from arteries
They only have an endothelium supported by mural cells and a basement membrane
State 3 functions of the vascular endothelium
Promotes tissue homeostasis and regeneration (it is a source of angiocrine factors) Permeability Inflammation Haemostasis and thrombosis Angiogenesis Vascular tone
What evidence is there that vascular endothelium promotes tissue homeostasis?
damage of endothelium can cause end-organ dysfunction
State 4 diseases in which the vascular endothelium is dysfunctional
Cancer, diabetes, chronic inflammatory diseases, ischemia, atherosclerosis
Endothelial cells form a flat monolayer and have cell-cell junctions. Tell each other to stop proliferating. This is called ____ _____
contact inhibition
In which type of blood vessel do the majority of endothelial cells reside?
capillary
What responses do you see in an activated epithelium?
Pro-inflammatory, pro-thrombotic, pro-angiogenic
In the resting state you get anti-inflammatory etc
State 4 risk factors for atherosclerosis
Hypertension, Diabetes, Hypercholesterolaemia, Sex hormone imbalance, Ageing
Infectious agents, Proinflammatory cytokines, Oxidative stress
Environmental toxins, Heamodynamic forces
State the 4 Mechanisms contributing to atherosclerosis
- Leukocyte recruitment
- Permeability
- Shear stress
- Angiogenesis
Describe how Leukocyte recruitment contributes to atherosclerosis
- Leukocyte adhere to endothelium of large arteries and get stuck in sub-endothelial space. They differentiate into macrophages and foam cells
- In a normal person leukocytes would adhere to endothelium of post-capillary venules and transmigrate into tissues
Describe how Permeability contributes to atherosclerosis
- Increased permeability causes leakage of plasma proteins into sub-endothelial space
- LDLs sticks to proteoglycans and is oxidised by free radicals
- Macrophage engulf oxidised LDLs and form foam cells (fatty streak formation)
Describe how shear stress contributes to atherosclerosis
- Atherosclerotic plaques occur preferentially at bifurcations and curvatures of vasculature
- This is because blood flow is disturbed. Irregular distribution of low wall sher stress
- Disturbed blood flow promotes thrombosis, inflammation, endothelial apoptosis, SMC proliferation, loss of NO production!!!!
Describe how angiogenesis contributes to atherosclerosis
It is triggered by hypoxia
Endothelial cell migration, proliferation and formation of new vessel sprouting out from old
It promotes plaque growth
state 1 reason why NO is essential for cardiovascular health?
Dilates blood vessels, reduces platelet activation, reduces proliferation of SMC, reduces release of superoxide radicals, reduces oxidation of LDL cholesterol
what mechanism is involved in the LATE stage of atherosclerotic plaques development?
angiogenesis
State ways in which the vascular endothelium plays a role in covid 19
- Increased circulating endothelial cells
- Cytokine storm -> activates the endothelium -> thrombi formation
Which risk factor for atherosclerosis hasnt been reduced over the last decade through medication?
diabetes
State 2 complications of an advanced atherosclerotic plaque
plaque rupture, stenosis
What is the main function of T lymphocytes in atherosclerosis
macrophage activation
State a function of vascular smooth muscle in atherosclerosis?
Migration and proliferation - formation of fibrous cap
state 5 functions of macrophages in atherosclerosis
- Foam cell formation
- Cytokine release (IL-1) and chemokine release (MCP-1)
- Source of free radicals - oxidative enzymes like NADPH oxidase and Myeloperoxidase needed for free radical generation - radicals further oxidise LDL
- Growth factor release - PDGF + TGF-b - causes VSMC proliferation and extracellular matrix deposition (fibrous cap formation)
- Express Metalloproteinases - lead to plaque erosion/rupture -> occlusive thrombus
State 2 functions of vascular endothelial cells in atherosclerosis
Barrier function - to lipoproteins
Leukocyte recruitment
Macrophage specific protein CD68 stains___ colour?
brown
What role does OXIDISED LDL play in atherosclerosis?
Chronic Inflammation - damages epithelium and smooth muscle. Also phagocytosed by macrophages which triggers inflammation
In Familial hyperlipidemia, there is a deficiency of LDL ___. LDL levels climb. __ receptors on macrophages cause them to accumulate OXIDISED LDL. Xanthomas form and contain _ cells. An associated disease is _.
Receptors
Scavenger
Foam
Atherosclerosis
Compare and contrast macrophage scavenger receptor A and B
A= CD204 B = CD36
A binds to gram+ bacteria, B binds to malaria parasites
Both bind to oxidised LDL and dead cells
What are the findings in a vulnerable atherosclerotic plaque?
Thin fibrous cap, reduced VSMC and collagen, infiltrate of activated macrophages expressing MMPs, large eccentric lipid rich necrotic core
What causes macrophage apoptosis in atherosclerosis and what happens after?
Toxic oxidised LDL derivatives
Lipids are released into lipid necrotic core
What transcription factor is the “master” regulation of inflammation?
NFkB
What are the signs and symptoms of ischemic heart disease?
angina chest pain - can radiate to arms, back, jaw, neck, shoulder
High or low bp, syncope
Heart rhythm problems
General important signs - leg swelling, reduced exercise capacity, diaphoresis, nausea, fatigue, SOB, dizziness
What are the risk factors of ischemic heart disease
non - modifiable - age, gender (more in male), ethnicity(more in eastern european), genetic evidence, family history, previous history of CVD
Modifiable - high blood pressure, cholesterol, smoking, alcohol, diabetes, bmi, diet, low socio-economic background, stress
What is the greatest risk factor for IHD?
diet
An atherosclerotic plaque is mainly made of?
fibrous tissue
State 3 things that cause obstruction of coronary blood flow
- Atheroma
- Thrombosis
- Spasm
- Embolus
- Coronary ostial stenosis
- Coronary arteritis
Describe the different ways in which a patient with IHD can present
Asymptomatic Chronic stable angina Acute Coronary Syndromes - Unstable angina, NSTEMI, STEMI Heart Failure Sudden Death
When atherosclerotic plaque breaks and becomes in contact with blood. State 3 ways in which thrombus could form
Fibrin deposition
RBCs entrapped
Blood platelets adhere to it
During hypoxia. ___ in the heart dilate. It is more effective in __ atherosclerosis than chronic.
collaterals
acute
In the late staves of MI, Vessels walls ___ increases, fluid leak and local tissue oedematous. Cardiac muscle cells swell and due to no blood supply die within few hours
permeability
State 2 causes of death after a MI
- Decreased cardiac output-systolic stretch and cardiac shock
- Damming of blood in body’s venous system
- Ventricular fibrillation
- Rupture of infarcted area
Differentiate between the effect on muscle of small vs large area ischemia
Small area - centre of lesion is temporarily non functional
Large area - centre is dead, surrounding non-functional tissue
State a risk assessment tool used for IHD
JBS3, QRISK*3
how do you diagnose IHD?
Clinical history and symptoms - e.g. chest pain
Serum markers of cardiac event - troponin, LDH, CK, AST
lipid profile
Clinical examinations - heart auscultation, BP, BMI, GPE
Biomarkers for predicting death - BNP, CRP, Renin, ACR
ECG
Echocardiography (transesophageal can be used to assess for aortic dissection)
Coronary angiography
US and doppler velocity probes - ultrasonography of common and internal carotid arteries.
ECG findings in stable angina?
Normal - ST depression only during stress test
ECG findings in unstable angina and NSTEMI?
Both have ST depression and T wave inversion
Only NSTEMI has elevated Troponins
ECGG in acute MI/STEMI
ST segment elevation with T wave inversion.
Q waves
state 3 pharmacological treatments for IHD
HMG-Coa reductase inhibitors Bile acid sequestrants CCBS, ACE inhibitors Beta blockers Anti-anginal agents Platelet aggregation inhibitors Nitrates
State 2 surgical treatments for IHD
PCI and CABG
Which 3 features must be present in typical angina?
Precipitated by physical exertion
Constricting discomfort in the front of the chest, neck, shoulders, jaw or arms
Relieved by rest or GTN within 5 minutes
What 3 features must be present in atypical angina?
2 features in typical angina
Plus GI discomfort and/or breathlessness and or nausea
Pain associated with dizziness, palpitations, tingling, difficulty swallowing or brought on by breathing is ___ to be stable angina
unlikely
A 64 year old man presents with increasing breathlessness and chest pain on exertion. what are the differentials?
- Pulmonary - Asthma, copd, pulmonary embolism
- Cardiovascular - Stable angina, unstable angina, pericarditis
- GI -Heartburn
- MSK
__ angina occurs when resting, lasts longer than stable, rest and medicine don’t relive it, can get worse over time/lead to MI
unstable
__ angina is caused by a spasm in coronary artery due to cold, stress, smoking
Prinzmetal/Variant/Vasospastic
why is it important to check troponin levels when a patient presents with increasing breathlessness and chest pain on exercise for instance? how do you interpret the troponin results?
Troponin rises after 4 hours of MI and is elevated for up to two weeks
If troponin levels are normal - less likely symptoms due to heart muscle damage. Stable angina more likely.
Rise and or fall in series of troponin indicates heart attack
what is the first line treatment for stable angina?
- short acting nitrate (e..g sublingual nitrogen) + B blocker OR CCB
Low heart rate (<60) - consider DHP CCB
symptoms remain uncontrolled - consider B-blocker + DHP CCB
what is the second line treatment for stable angina if first line fails?
long acting nitrate ivabradine nicorandil ranolazine trimetazidine
if these fail - consider revascularisation
ST elevation in leads 1, aVL and V6
Reciprocal changes - ST depression in inferior leads (III and aVF)
what is your diagnosis?
Lateral STEMI
Table ST segment elevation, reciprocal changes, coronary artery involved and type of MI
refer to notes
ST depression leads 2,3. T wave inversions.
what is your diagnosis?
NSTEMI or Unstable Angina
What is the 1st line management for a STEMI?
- antiplatelet and anticoagulant therapy
- reperfusion - PCI first line
- long term management (antiplatelets, B-blocker, statin, ACE inhibitor)
How would you treat NSTEMI and Unstable angina?
- If patient is unstable, has positive troponin or ST changes = high risk - PCI, CABG
- If patient is low risk. perform stress ECG. Positive stress ECG - coronary angiography, PCI, CABG
why does sublingual glycerol trinitrate alleviate stable angina?
vasodilation increases blood supply
describe the mechanism of digoxin. what is it used to treat?
Digoxin inhibits the Na+/K+ exchange ATPase on cardiac myocytes and nodal tissue.
Competes for K+ binding site. Increases heart contractility. Decreases heart rate.
atrial fibrillation, Heart failure
why are potassium blood levels important when a patient is on digoxin?
Hypokalemia means more digoxin binding (less competition by K+) . Enhanced therapeutic and adverse effects of digoxin (heart block)
Hyperkalemia (e.g. in kidney disease) -> reduced clearance -> more digoxin
