Cardio Flashcards
Ischemic heart disease
Imbalance between myocardial oxygen supply and demand resulting in myocardial hypoxia.
Myocardial oxygen supply depends on:
- O2 content:
1) Hemoglobin
2) systemic oxygenation - Coronary blood flow:
1) coronary perfusion pressure - diastolic BP (reduced by hypotension)
2) coronary vascular resistance -
a) external compression: myocardium on coronaries
b) intrinsic regulation: auto-regulation to increase blood flow
Myocardial oxygen demand depends on:
- Ventricular Wall stress (P x r/2h)
Increase pressure causes an increased wall stress which needs and increased oxygen demand. (Hypertension, aortic stenosis) - Heart rate
Increased HR needs more energy and so needs more oxygen. (Exercise, stimulants) - Contractility strength
Increased contraction force needs more energy and therefore more oxygen. (Catecholamines, ionotropic medications)
Intrinsic auto regulation involving metabolic factors:
- Hypoxemia impairs ATP production which increases ADP,AMP which increases adenosine and that causes vasodilation and so increases coronary perfusion.
- Factors like lactate or hydrogen ions can increase perfusion.
Intrinsic auto regulation involving endothelial factors:
- Nitric oxide, prostacyclin, and EDPF are factors that can increase perfusion.
Endothelin 1 is a
Vasoconstrictor
Intrinsic auto regulation involving neural factors:
Alpha adrenergic receptors - vasoconstrict
Beta2 adrenergic receptors - vasodilate
Patho physiology of ischemia
Fixed plaques + abnormal vascular tone -> narrow lumen -> low myocardial supply
Abnormal vascular tone:
1) inappropriate vasoconstriction: dysfunctional endothelium not releasing vasodilators
2) loss of normal anti thrombotic properties:
Dysfunctional endothelium
Factors that reduce myocardial oxygen supply:
Hypotension
Anemia
Massive bleeding
Sepsis
Factors that increase myocardial oxygen demand:
Tachycardia
Arrhythmia
Severe aortic stenosis
Metabolic syndrome:
Having any 3 of:
Hypertension High triglycerides Low HDL cholesterol Diabetes Obesity
What is Acute coronary syndrome and what does it depend on?
Plaque disruption followed by platelet aggregation and thrombus formation
Depends on the degree of blockage and ischemia
Site of atherosclerosis, hypertension, vasculitis:
Atherosclerosis site are the elastic and muscular arteries
Hypertension site are small muscular arteries and arterioles.
Vasculitis affect different vascular segments.
Vasculogenesis occurs in:
Using what factor:
Happens in embryogenesis by VEGF
Angiogenesis, neovascularisation
Occur after maturity in inflammation or in cancers (neoplasia)
Arteriogenesis
Remodeling of existing arteries in response to chronic changes in pressure or flow
Tight endothelial cell junctions can loosen under the influence of:
What does this lead to:
High blood pressure or vasoactive agents (histamine in inflammation)
Flooding of adjacent tissues by electrolytes and protein and even leukocytes can slip between endothelial cells in case of inflammation.
Comment on Endothelial permeability in liver sinusoids, renal glomeruli, and the central nervous system:
Liver and renal are fenestrated
While the CNS is impermeable BBB
Intimal thickening of the vessels happens due to:
1) endothelial cell response
2) vascular smooth muscle response
List the Promoters of proliferative activities of smooth muscles:
PDGF Endothelin-1 Thrombin Fibroblast growth factor Interferon gamma Interleukin 1
List the inhibitors of smooth muscle proliferative activities:
Heparan sulfates
Nitric oxide
TGF-B
Regulators of the smooth muscle proliferative activities include:
RAAS
Catecholamines
Estrogen receptor
Osteopontin which is component of the ECM
What happens to the arteriolar wall with Benign hypertension?
What is the kidney appearance?
Hyaline arteriolosclerosis
The wall is thickened with increased protein deposition (hyalinized) and the lumen is narrowed.
This is chronic
Kidney appears leathery
What impact does benign hypertension have on kidneys?
The kidney get a condition called benign nephrosclerosis due to hypertension.
What happens to the arteriolar wall with the malignant hypertension?
What is the kidney appearance?
Hyperplastic arteriolosclerosis
The smooth-muscle hyperproliferates and produces an onion skin like appearance.
Acute repeated spikes of uncontrolled blood pressure
Kidney appears flea bitten
What is Fibroelastic hyperplasia?
Laying down thin fibers of collagen and elastin and happens due to aging.
Further stage of malignant hypertension includes:
Necrotizing arteriolitis
Comment on endothelial activation and endothelial dysfunction:
Endothelial activation occurs when normal conditions like normotension, laminar flow, constant growth factors and they maintain a nonthrombotic interface with smooth muscle cells.
Endothelial dysfunction occurs when excessive stimulation by normal physiologic pathways.
Arteriolosclerosis
Hardening of the small arteries and arterioles and may cause ischemic injury.
Monckeberg medial sclerosis
Calcific deposits in muscular arteries in people older than 50.
Not clinically significant
Atherosclerosis
Gruel + hardening
Most frequent and clinically important pattern.
Atherosclerosis components:
Has a fibrous cap (smooth muscle cells, macrophages, lymphocytes, collagen, elastin, proteoglycans) with a necrotic center (cell debris, cholesterol crystals, foam cells, calcium)
What is a fatty streak?
Describe on tissue:
It is a collection of foamy macrophages in the intima
Appears like the endothelial cells are lifted above and there is space/foaminess.
Explain Vulnerable plaque and Stable plaque:
Vulnerable plaques are more prone to rupture as they have thin fibrous caps and large lipid cores and increased inflammation
Stable plaques have densely collagenous and thickened fibrous caps with minimal inflammation so they are more stable and less likely to rupture.
Consequences of atherosclerosis include:
MI - heart attack
cerebral infarction - stroke
Aortic aneurysms
Peripheral vascular disease - gangrene
Presence of ST elevation and increased bio marker levels indicates:
Full block of the artery
STEMI
Last stage of acute coronary syndrome
ST segment changes (T wave inversion, ST depression, no Q waves) and no increase in bio marker levels indicates:
Unstable angina
ST segment changes( T wave inversion, ST depression, no Q waves) and an increase in bio marker levels indicates:
NSTEMI
consequences of myocardial infarction include:
A decrease in contractility which causes hypotension which causes ischaemia - cardiogenic shock
Ventricular thrombus - embolism
Electrical instability - arrhythmias
Tissue necrosis - congestive heart failure, cardiac tamponade, and pericarditis.
Ventricular thrombus consequences include:
A thrombus in the left ventricle which can detach and cause astroke.
1st line of angina relief is to use:
-short acting nitrates
Plus
-Beta blockers/CCB both reduce the heart rate
-Consider CCB-DHP if low heart rate or patient is intolerant to Beta blockers/contraindications
-Consider BB + CCB-DHP if angina class 2 or more
2nd line of angina relief is to use:
- Long acting nitrates
- Ivabradine
- Nicorandil
- Ranolazine
- Trimetazidine
Drugs that reduce HR:
- BB
- Ivabradine
- Verapamil and Diltiazem
Drugs that induce vascular smooth muscle relaxation:
- Dihydropyridine CCB
- Nitrates
- Nicorandil
List Drugs that are metabolic modulators; and how do they work:
- Trimetazidine = increases cell tolerance to ischemia by inhibiting long chain ketoacyl enzyme A thiolase and this increases the anaerobic glucose metabolism.
- Ranolazine = causes an inhibition of the late sodium current thus preventing calcium overload during ischemia and so resulting in the distribution of myocardial bloodflow towards the ischaemic areas with a reduction of ischaemia.
Medications for event prevention of the coronary artery disease:
- Antiplatelet agents like aspirin and clopidogrel
- Lipid lowering agents like statins
- Renin angiotensin aldosterone system blockers that reduce the total mortality/MI/stroke/HF among patients with diabetes/PAD/HF
In antiplatelet therapies what medication inhibits the COX to prevent thromboxane formation and thus prevent platelet formation?
Aspirin
In antiplatelet therapies what medication prevents the entry of ADP(energy supply) into the platelet? (Inhibitors of P2Y12 receptor)
Ticlopidine Clopidogrel Prasugrel Ticagrelor Cangrelor Elinogrel
In antiplatelet therapies what medication is used to prevent thrombin from binding to its receptor on the platelet? (Inhibitor of PAR1)
Bivalurudin
Hirudin
Argotraban
In antiplatelet therapies what medication is used to prevent GP IIb/IIIa to bind to its fibrinogen receptor?
Abciximab
Eptifibatide
Tirofiban
What is heart failure?
Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that in pairs the ability of the ventricles to fill or eject blood.
HFrEF is known as:
Explain:
Systolic dysfunction due to a dilated chamber and therefore has decreased wall motion and so this means that there is an increase in the left ventricular end-diastolic volume.
(Left ventricular injection fraction is less than it equal to 40%)
HFpEF is know as:
Explain:
Diastolic dysfunction of a normal sized chamber with normal emptying but has impaired filling.
Common causes that can lead to heart failure; and what is the most common one:
Hypertension Cardiomyopathies Valvular disease Coronary heart disease - most common Congenital heart disease Pericardial disease Infiltrative disorders
Frank-Starling law of the heart:
(It is a compensatory mechanism in HF)
Increased end-diastolic fiber length, volume, and pressure causes an increase in ventricular performance.
Compensatory mechanism in HF by neurohormonal activation:
-Sympathetic nervous system Increase in HR Increased myocardial contractile simulation Increased rate of relaxation -RAAS Sodium and water retention -Natriuretic peptide system
What is used as an indicator for HF?
BNB
The more BNB the worse the HF.
What is ARNI (Entresto)?
It is a combination of valsartan and Sacubitril and this is the new medication of HF.
Angiotensin II is blocked by valsartan
Neprilysin is blocked by Sacubitril
What is the dominant cause of IHD syndromes and it is due to:
The dominant cause of the IHD syndrome is insufficient coronary perfusion relative to myocardial demand and happens due to:
- chronic progressive atherosclerosis
- variable degrees of superimposed acute plaque change, thrombosis, and vasospasm.
What is Prinzmetal variant angina?
Uncommon coronary artery spasm, The anginal attacks are unrelated to physical activity, heart rate, or blood pressure
What is Stable angina (typical angina pectoris)?
An imbalance in coronary perfusion (due to chronic stenosing coronary atherosclerosis) relative to myocardial demand such is that produced by physical activity emotional excitement or any other cause of increased cardiac workload.
What is Unstable or crescendo angina:
A pattern of increasingly frequent pain often of prolonged duration that is precipitated by progressively lower levels of physical activity or even occurs at rest.
What is the time frame for reversible injury?
0-1/2hr
Visible from electron microscope - relaxation of myofibrils, mitochondrial swelling, glycogen loss
What myocyte proteins are released in myocardial infarction and can be used as diagnostic indicators?
- CK-MB
- Troponin — best one
- Myoglobin
