Cardiovascular Flashcards
Stimulation of what receptor increases cAMP in cardiac myocytes?
B1
Stimulation of what receptor increases cAMP in vascular smooth muscle cells?
B2
What is the most common cause of coronary sinus dilation?
Elevated right sided heart pressure secondary to pulmonary artery hypertension.
How does moderate coarctation of the aorta present?
In childhood or adolescence with symptoms of lower extremity claudication, blood pressure discrepancy between the upper and lower extremities, and delayed or diminished femoral pulses. May also present with continuous murmurs and pulsatile intercostal collaterals.
What is the mechanism of action of Daptomycin?
It disrupts the bacterial membrane through the creation of transmembrane channels. This causes leakage of intracellular ions leading to depolarization of the cellular membrane and inhibition of macromolecular synthesis and cell death.
What is daptomycin used to treat?
Gram positive organisms- used for treating skin and skin structure infections and bacteremia (with or without endocarditis) due to Staph aureus, including MRSA.
What are the side effects of daptomycin?
Increased CPK, increased incidence of myopathy
Persistent lymphedema with chronic dilation of lymphatic channels predisposes patients to the development of what condition?
Lymphangiosarcoma, a rare malignant neoplasm of the endothelial lining or lymphatic channels.
What is a common complication of transmural myocardial infarction 3-7 days after the onset of total ischemia?
Ruptured LV free wall.
What causes LV free wall rupture following transmural MI?
Coagulative necrosis, neutrophil infiltration, enzymatic lysis of connective tissue substantially weaken the infarcted myocardium.
What three symptoms are characteristic of pericardial tamponade?
Muffled heart sounds, elevated JVP, profound hypotension.
What structures are obstructed in Hypertrophic Cardiomyopathy (HOCM)?
Mitral valve cusp and intraventricular septum. This obstruction is due to abnormal systolic anterior motion of the anterior leaflet of the mitral valve towards a hypertrophied interventricular septum
Describe the genetic inheritance of HOCM and the genes that are mutated.
Autosomal dominant. Mutation in genes for sarcomere proteins (components of thick or thin filaments).
What are the typical presenting symptoms in a patient with HOCM?
Exertional syncope, harsh systolic murmur, asymmetric septal hypertrophy
What murmur is heard in a patient with HOCM?
Systolic ejection murmur
In systolic dysfunction, describe the pathology of heart failure.
Increased blood volume in the heart causes stretching of the atria and ventricles beyond the appropriate stretch to cause maximal contraction by Starling mechanism.
Increased myocardial stretch causes release of what proteins?
ANP from the walls of the atria; BNP from the walls of the ventricles. They both act to activate guanylate cyclase which induces increase in cGMP.
What condition is implicated by an S3 gallop?
Increased left ventricular filling rate during mid diastole or mitral regurgitation.
What is the most common anatomic abnormality that produces mitral regurgitation?
Myxomatous degeneration due to mitral valve prolapse.
Describe the murmur associated with aortic stenosis.
Systolic ejection type crescendo decrescendo murmur.
What determines the intensity of an aortic stenosis murmur?
Intensity is proportional to the magnitude of the left ventricle-to-aorta pressure gradient during systole.
Define sudden cardiac death.
Cardiac arrest that begins within 1 hour of a precipitating event and that ultimately proves fatal.
What induces arrythmias in patients with CAD?
Ischemia that induces electrical instability and a potentially lethal arrythmia.
What is the best indication of severity in mitral regurgitation?
The presence of an S3 gallop. This reflects an increased rate of LV filling due to a large volume of regurgitant flow re-entering the ventricle during mid diastole.
What is the best indication of severity of mitral stenosis?
The S2 (closure of the aortic valve) to opening snap interval.
What is cystic medial degeneration?
Myxomatous changes in the media of large arteries. It is characterized by fragmentation of elastic tissue and by separation of the elastic and fibromuscular components of the tunica media by small, cleft like spaces that become filled with amorphous ECM.
What is the role of lysyl oxidase in maintaining vascular integrity?
It cross links elastin and collagen fibers. It is responsible for maintaining the elastic lamina and ensuring aortic integrity.
From where is energy for myocardial cellular function derived?
Glycolysis, oxidation, fatty acid oxidation.
Which process produces the greatest amount of ATP for myocardial function but also requires the most oxygen?
Fatty acid oxidation. It is the main source of energy production.
What type of collagen is the most prevalent collagen in mature scars?
Type I collagen.
Name the three potassium sparing diuretics
Amiloride, triamterene, spironolactone
How does digoxin alter conduction through the AV node?
It induces stimulation of the AV node by the vagus nerve causing a slowing of conduction through the AV node
What are the symptoms of digoxin toxicity?
Fatigue, blurry vision, changes in colour perception, nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, confusion, delirium
How is heart rate affected in digoxin toxicity?
Bradycardia followed by junctional escape beats, sustained junctional escape rhythms and eventually ventricular tachycardia or fibrillation.
What electrolyte abnormalities are present with digoxin toxicity?
Elevated plasma K+.
What increases a patient’s susceptibility to digoxin toxicity?
Hypokalemia
In patients with stable angina, what effect do nitrates have?
Decrease cardiac preload, cardiac work, and cardiac oxygen demand via venodilation.
What physiological changes occur in the heart in response to normal aging?
Decreased LV chamber size, (esp. in apex to base dimension), sigmoid shape of the ventricular septum; myocardial atrophy with increased interstitial connective tissue and accumulation of cytoplasmic granules containing brownish lipofucin pigment within cardiomyocytes.
What causes localized amyloidosis confined to the cardiac atria?
Deposition of abnormally folded ANP derived proteins. The incidence of this increases with age.
What is a risk associated with senile cardiac amyloidosis?
Atrial fibrillation.
What protein is responsible for amyloidosis in the thyroid gland?
Calcitonin
What protein is responsible for amyloidosis in the pancreatic islet cells?
Islet amyloid protein (amylin)
What protein is responsible for amyloidosis in the cerebrum/ cerebral blood vessels?
B-amyloid protein
What protein is responsible for amyloidosis in the pituitary gland?
Prolactin.
What causes multi-organ amyloid deposition in primary systemic amyloidosis?
Immune globulin light chains.
What is considered the primary event in the process leading to aortic dissection?
A tear in the tunica intima
What is the greatest risk factor for the development of intimal tears leading to aortic dissection?
Hypertension
How do ANP and NO exert intracellular effects?
By binding a receptor protein with guanylate cyclase enzymatic activity to set off the cGMP messenger system
What is the mechanism of action of sildenafil?
To increase intracellular cGMP concentration by inhibiting cGMP phosphodiesterase in target cells.
Name three conditions caused by abnormal migration of neural crest cells through the primitive truncus arteriosus and bulbus cordis.
Tetralogy of Fallot, transposition of the great vessels, truncus arteriosus.
Hemodynamic actions of epinephrine occur secondary to agonistic effects at what receptors?
a1, b1, b2
Stimulation of a1 has what response on blood pressure?
Increased total peripheral resistance and increased blood pressure.
Stimulation of b2 receptors have what response on vasculature of skeletal muscle?
Vasodilation and decreased bp.
How do effects of a1 and b2 vary across different doses of epinephrine?
B2 mediated effect predominates at low doses; a1 effect predominates at higher doses.
How does stimulation of b1 receptors alter heart muscle?
Increased heart rate and contractility.
What are the side effects associated with adenosine?
Flushing, chest burning, hypotension, high grade AV block
What symptoms are characteristic of atrial myxoma?
Constitutional symptoms, a mid-diastolic rumbling murmur heard best at the apex, positional dyspnea, and a large pedunculated mass in the left atrium. They often present with emboli.
What is the most common primary cardiac neoplasm and where do most arise?
Myxomas; 80% occur in the LA.
Describe the histology associated with a myxoma tumor.
Scattered cells within a mucopolysaccharide stroma, abnormal blood vessels, hemorrhaging
What is produced by myxoma tumors?
VEGF- causing angiogenesis, hemorrhaging, and friability. IL-6- causes constitutional symptoms
What causes symptoms in cardiac myxoma?
Valve obstruction.
Orthopnea is a sign of what condition?
Advanced left sided heart failure or mitral stenosis
Bilateral lower extremity edema and congestive hepatomeagly are characterisitc of what condition?
Right sided heart failure.
What is the most specific symptom of giant cell arteritis?
Jaw claudication
What is demonstrated on temporal artery biopsy in a patient with giant cell arteritis?
Granulomatous inflammation of the media
What structures are typically effected in Takayasu arteritis?
Aortic arch and sometime the remainder of the aorta and its branches.
Describe blood pressure changes that may accompany Takayasu arteritis.
Lower bp and pulses in the upper extremities and cold or numb fingers.
In what conditions do iron containing proteins and erythrocytes extravasate into alveoli?
In the event of increased intravascular pressure.
What pathological conditions are associated with hemosiderin-contataining alveolar macrophages?
Heart failure cells- indicate episodes of previous pulmonary congestion and edema associated with chronic left sided heart failure.
Hemosideren laden macrophages respond in what way to the Prussian blue stain?
Cytoplasmic granules turn dark blue
A child with a low pitched holosystolic murmur heard best at the left sternal border with accentuation during the handgrip exercise, has what condition?
Ventricular septal defect.
Why does a murmur associated with a VSD increase in intensity when valsalving?
Increases afterload which increases the L-R shunt.
What antihypertensive agent has minimal effect on AV conduction?
Nifedipine.
Nifedipine is a useful drug in what specific subgroup of patients?
Patients with bradycardia- it causes peripheral vasodilation and reflex tachycardia.
Cyanotic toe discoloration and renal failure in an elderly patient following an invasive vascular procedure is characteristic of what condition?
Atheroembolic disease of the renal arteries. This is caused by cholesterol containing debris that gets lodged into smaller and smaller vessels and causing ischemia of organs and tissues.
In a patient with atheroembolic disease of the renal arteries, biopsy shows what?
Needle shaped cholesterol crystals that partially or completely obstruct renal arterioles.
What is normal pressure (min and max) for the right atrium?
min-0; max-8 mmHg
What is normal pressure (min and max) for the right ventricle?
min-4; max-25 mmHg
What is the normal pressure (min and max) for the pulmonary artery?
min-9; max-25 mmHg
What is normal pressure (min and max) for the left atrium?
min-2 max-12 mmHg
What is normal pressure (min and max) for the left ventricle?
min-9; max- 130 mmHg
What is normal pressure (min and max) for the aorta?
min-70; max- 130 mmHg
What are the five Ts of cyanotic congenital heart disease?
Tetrology of fallot, tricuspid atresia, transposition of the great vessels, truncus arteriosus, total anomalous pulmonary venous return.
Name four non-cyanotic congenital heart diseases.
ASD, VSD, PDA, aortic coarctation.
What abnormalities characterize tetrology of fallot?
Pulmonic stenosis, VSD, RV hypertrophy, overriding aorta
How does digoxin cause increased parasympathetic tone?
Through action on the vagus nerve which leads to a decreased rate of AV conduction.
What causes reperfusion injury?
oxygen free radical generation by parenchymal cells, endothelial cells and leukocytes; severe irreversible mitochondrial damage; inflammation and circulating neutrophils; activation of complement.
What pathologic condition is associated with a wide pulse pressure?
Aortic regurgitation
Findings of thick fibrous tissue in the pericardial space is diagnostic for what condition?
Constrictive pericarditis.
What pathologic states occur as a result of constrictive pericarditis?
Low CO and right sided heart failure. May cause a pericardial knock (which occurs before S3)
What is Kussmaul sign?
A paradoxical rise in JVP during inspiration. This occurs because the volume restricted right ventricle is unable to accommodate the inspiratory increase in venous return.
From what vascular structures does the right brachiocephalic vein arise?
The union of the right subclavian vein and the right internal jugular vein. The right external jugular drains into the right subclavian. The right brachiocephalic vein also drains the right lymphatic duct.
What is drained by the right lymphatic duct?
Lymph from the right upper extremity, right face and neck, right hemithorax, right upper quadrant of the abdomen.
What does the brachiocephalic vein drain?
Ipsilateral jugular and subclavian veins
Which vessels combine to form the SVC?
Bilateral brachiocephalic veins
What is another name for thromboangiitis obliterans?
Buerger’s disease
What is Buerger’s disease?
Vasculitis of medium and small sized arteries, principally the tibial and radial arteries.
Describe the pattern of inflammation in Buerger’s diseae?
Segmental thrombosing vasculitis that often extends into contiguous veins and nerves, encasing them in fibrous tissue.
What may cause Buerger’s disease?
Direct endothelial cell toxicity from tobacco products or hypersensitivity to them. It is often seen among heavy smokers at a young age.
What symptoms and complications are associated with Buerger’s disease?
Claudication, superficial nodular phlebitis, cold sensitivity; also distal pain, and ultimately it can cause ulcerations and gangrene of the toes, feet, or fingers.
Fibrous intimal thickening with endocardial plaques limited to the right heart are characteristic of what disease?
Carcinoid heart disease associated with carcinoid syndrome. It may cause pulmonic stenosis and restrictive cardiomyopathy.
What determines the degree of fibrosis (i.e severity of disease) in a patient with carcinoid heart disease?
Plasma levels of serotonin and urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid.
Describe the murmur associated with a VSD.
holosystolic murmur loudest over the mid sternal border.
What is the most common cause of death in lightning injury?
Fatal arrythmias and respiratory failure.
What do jugular venous pressure tracings measure?
right atrial pressure.
What is the first peak on a jugular venous pressure tracing and in what condition is it absent?
a-wave; it is generated by atrial contraction and is absent in patients with a-fib.
What is Wolff-Parkinson-White syndrome?
A pre-excitation syndrome with re-entry circuits that cause paroxysmal, narrow QRS complexes (supraventricular tachycardia).
What EKG findings are characteristic of Wolff-Parkinson-White syndrome?
Shortened PR interval with an early upslope (delta wave) at the start of each ORS complex. QRS is also widened but becomes narrow during tachyarrhythmia.
From what pharyngeal and aortic arch is the common carotid derived?
3rd.
How is arteriolar resistance affected in left sided CHF?
It increases due to decreased CO. RAAS activation and increased sympathetic output raise resistance and exascerbate heart failure.
What is Ebstein’s anomaly?
Apical displacement of the tricuspid valve leaflets, decreased volume of the right ventricle and atrialization of the right ventricle
What medication is associated with Ebstein’s anomaly?
Lithium
What is a cystic hygroma?
A tumor most commonly located on the neck apparent at birth. It may also cause swelling of the hands and feet.
Cystic hygromas are associated with what condition?
Turner’s syndrome.
What type of drug is amiodarone?
A class III antiarrhythmic drug used for arrythmias.
What is the mechanism of action of class III antiarrythmatics?
Block outward current of potassium during phase 3 of the AP.
What classes of drugs prolong the cardiac action potential?
Class 1A and III antiarrythmatics.
What may occur as a consequence of prolonged QT?
Torsades de points a form of ventricular tachycardia.
Which drug prolongs the QT interval but has a low risk of Torsades de Pointes?
Amiodarone.
Which macrolide does not have a significant effect on the CYP450 system?
Azithromycin
Which statin is not metabolized by the CYP450 system?
Pravastatin.
How do the effects of dopamine vary with dose?
At lower doses, it stimulates D1 receptors in the renal vasculature and tubules which increases GFR, RBF, and Na excretion. It also causes mesenteric vasodilation. At higher doses, it stimulates b1 receptors in the heart which increases contractility, pulse pressure, and systolic bp (diastolic bp is usually unchanged). At even higher doses, dopamine stimulates a1 receptors in systemic vasculature causing vasoconstriction and thus decreased CO due to increased afterload.
Which adrenergic agonist increases renal blood flow at moderate doses?
Dopamine
Thiazide diuretics cause elevations in what agents?
Serum LDL, calcium, uric acid, glucose.
Thiazide diuretics lower what agents?
Serum K, Na, and bp.
What is the mechanism of action of Fenoldopam?
It is a benazepine derivative of dopamine. It is a selective dopamine-1 receptor agonist with no effect on alpha or beta receptors. It activates adenylyl cyclase and raises cAMP resulting in vasodilation of most arterial beds.
What does Fenoldopam do?
It decreases systemic vascular resistance, improves RBF, and causes increased sodium and water excretion. It is administered IV.
For what condition is Fenoldopam indicated?
Short term management of severe hypertension
What are some common side effects of nitrates?
cutaneous flushing, headaches due to vasodilation.
What is first line therapy to lower LDL cholesterol in patients with concommittant low HDL?
HMG-CoA reductase inhibitors (statins)
The combination of what two drug classes in the treatment of hyperlipidemia increase risk for cholesterol gallstones?
Fibric acid derivatives and bile acid binding resins.
Name six antiarrythmic agents implicated in QT prolongation and torsades de pointes.
Quinidine, procainamide, disopyramide, ibutilide, dofetilide, sotalol.
What toxicity may be associated with nitroprusside and how can this be minimized in overdose?
Cyanide toxicity. Antidote is sodium thiosulfate which enhances CN metabolism and excretion.
What is the first line agent in treatment of hypertensive emergency?
Nitroprusside.
What are the clinical signs of cyanide toxicity?
altered mental status, lactic acidosis
What class of drugs does Sotalol belong to?
Has beta blocking and class 3 antiarrythmatic (K channel blocking) properties.
What EKG abnormalities are present in a patient taking sotalol?
Prolonged PR and QT intervals.
What complications are associated with varicose veins?
Painful thromboses, stasis dermatitis, skin ulcerations, poor wound healing, superficial infections.
What is phlegmasia alba dolens?
A consequence of iliofemoral venous thrombosis occurring in peripartum women.
Mitochondrial vaculoization is typically a sign of what type of injury?
Irreversible. Mitochondria become permanently unable to generate ATP.
The ABG results in a patient with a PE would show what?
Hypoxemia stimulates hyperventilation and respiratory alkalosis; pH would be increased and paCO2 would be reduced, PaO2 would be low.
What two agents most commonly cause infectious endocarditis?
S. aureus or S. viridans
Name three ways to decrease preload.
Sudden standing, valsalva, nitroglycerin.
Name three ways to increase preload and/or afterload.
Squatting, sustained hand grip, passive leg raise.
In a LV outflow obstruction murmur, what changes increase and decrease murmur intensity?
Decreased preload increases murmur intensity; increased preload decreases murmur intensity
What are some causes of diastolic heart failure?
Impaired myocardial relaxation or increased intrinsic ventricular wall stiffness.
How does diastolic heart failure shift the PV curve?
Upward and to the left to indicate decreased ventricular compliance. This reduces LVEDV for any given LVEDP
Ejection fraction LVEDP and LVEDV are changed in what way in diastolic heart failure?
Normal ejection fraction and LVEDV, but increased LVEDP.
What side effects are associated with Verapamil use?
bradycardia, AV nodal blocks, constipation, gingival hyperplasia. It is a negative ionotrope
Compare verapamil, nifedipine, and dilitazem in terms of their effects on the heart and on the vasculature.
Verapamil > dilitiazem > nifedipine on heart effects
Nifedipine > dilitazem > Verapamil on vasculature
What is the presentation of severe aortic stenosis?
SAD- syncope, angina, dyspnea
What is the most common cardiac manifestation of SLE?
Pericarditis.
How does pericarditis present?
As sharp, pleuritic chest pain that is relieved by sitting up and leaning forwards.
What is Trousseau Syndrome?
Tumor release of procoagulants causing migratory thrombophlebitis. It may be seen in patients with disseminated cancer.
Non bacterial thrombotic endocarditis entails what pathology?
Bland thrombus without accompanying inflammation or valvular damage
What causes non bacterial thrombotic endocarditis?
A hypercoaguable state or endothelial injury
Which types of cancers are associated with non bacterial thrombotic endocarditis?
mucinous adenocarcinomas of the pancreas, adenocarcinomas of the lung
The LAD and circumflex arteries supply what surfaces of the heart?
Anterior and left lateral surfaces
What does the posterior descending artery (a branch of the RCA) supply?
The inferior wall of the left ventricle which forms the diaphragmatic surface of the heart.
What causes obstruction of blood flow in claudication?
Atherosclerosis of large arteries caused by fixed stenotic atheromatous lesions.
Thigh claudication is suggestive of what type of occlusive disease?
Occlusion of the ipsilateral external iliac or common femoral artery and/ or both the superficial femoral and profunda femoris arteries.
Compromised blood flow to what vessels causes difficulty with sustaining an erection?
Aortoiliac atherosclerosis may diminish blood flow to the internal pudendal branches of the internal iliac artery causing difficulty sustaining an erection.
What structure is derived from the common cardinal veins?
The SVC
In an embryo, all veins drain into what cavity?
Sinus venosus which drains into the primitive atrium of the developing heart.
What are the three classes of embryonic veins and what do they become?
Vitelline- veins of the portal system; umbilical- degenerate; cardinal- veins of systemic circulation.
What causes hypercoagulability in adenocarcinomas?
Adenocarcinomas produce a thromboplastin like substance capable of causing chronic intravascular coagulations.
What causes acute Mitral regurgitation?
Rupture of chordae tendineae, infective endocarditis with destruction of valve leaflets, chordal rupture, ischemia or rupture of papillary muscles, failure of a prosthetic valve.
A combination of what antiarrythmatics may cause additive decrease in HR, AV node conduction, and myocardial contractility with bradycardia?
Non-dihydropyridine-type calcium channel blockers (verapamil, dilatiazem, etc.) and beta blockers.
What class of antiarrythmatics have the highest selectivity for ischemic myocardium compared to normal tissue?
Class IB antiarrythmatics (lidocaine). Amiodrone has now replaced lidocaine in management of ventricular tachycardia.
What type of drug prolongs the QRS complex in a rate dependent manner?
Drugs with strong use dependence such as Flecainide and other class 1C antiarrythmatics
What is the mechanism of action of class IC antiarrythmatics?
Binding to fast sodium channels of phase 0 depolarization. This blocks inward sodium current and prolongs QRS duration.
What is ‘use dependence’ of cardiac antiarrythmatics?
Prolonged sodium channel attachment which intensifies sodium blocking effects as heart rate increases due to less time between APs for the medication to dissociate from the receptor.
What class of antiarrythmatics demonstrate reverse use-dependence?
Class III- block repolarizing potassium current. The slower the heart rate, the more the QT interval is prolonged.
What is the mechanism of action of nitrate drugs?
NO stimulates guanylate cyclase to convert GTP into cyclic guanosine monophosphate (cGMP). This increase in cGMP coupled with decreased intracellular calcium decreases the activity of myosin light chain kinase and also decreases myosin light chain deposphorylation and smooth muscle relaxation.
How do you calculate maintenance dose?
(Cp(ss) x CL )/Bioavailability fraction (for IV, bioavailability fraction = 1)
What is the formula for half life?
(Vd x 0.7)/ CL
What is the formula for loading dose?
(Vd x Cp (ss))/ bioavailability fraction
Potassium sparing diuretics antagonize what factor?
The effects of aldosterone.
Pain radiating to the neck due to a cardiac process indicates possible ischemia in what region?
Inferior pericardium due to phrenic nerve supply.
Pericarditis several days following acute MI demonstrates what pathology?
Pericardial inflammation overlying the necrotic segment of myocardium
How do you treat pericarditis following MI?
Aspirin therapy for 1-3 days. It is self resolving.
What is Dressler’s syndrome?
Late onset post MI pericarditis that begins one week to a few months following MI. It is believed to be an autoimmune polyserositis.
What is the effect of inhibition of phosphodiesterase isoenzyme 3 in cardiac tissue?
It acts to metabolize cAMP which increases Ca2+ channel conductance in the SR which strengthens the force of contraction. Phosphodiesterases metabolize Ca in tissues.
In smooth muscle, what is the effect of increased cAMP?
Vasodilation.
How does left sided heart disease contribute to pulmonary hypertension?
It increases pulmonary venous pressure and congestion which leads to a passive increase in pulmonary arterial pressure, worsened by reactive vasoconstriction and structural remodeling of the pulmonary vasculature secondary to impaired NO availability and increased endothelin expression.
Why is liver infarction rare?
Due to its dual blood supply- portal vein and hepatic artery.
Rank the following according to susceptability to infarction following occlusion of a feeding artery: myocardium, kidney, liver, spleen, CNS.
CNS > myocardium > kidney > spleen > liver.
How does the law of conservation of mass apply to the steady state flow of an incompressible fluid through a system with varying cross sectional areas?
Total Flow = Flow Velocity x Cross sectional Area = constant
What embryologic failure causes transposition of the great arteries?
Failure of the fetal aorticopulmonary septum to spiral normally during septation of the truncus arteriosus.
Describe the murmur heard with aortic stenosis.
Harsh, crescendo-decrescendo systolic ejection murmur heard best in the right second intercostal space with radiation to the carotids.
What cardiac anomalies are associated with DiGeorge syndrome?
Tetrology of Fallot and aortic arch anomalies.
What cardiac anomalies are associated with Downs Syndrome?
Endocardial cushion defects (ostium primum ASD, regurgitant AV valves)
What cardiac anomalies are associated with Friedrich’s Ataxia?
Hypertrophic cardiomyopathy.
What cardiac anomalies are associated with Marfan’s?
Cystic medial necrosis of the aorta
What cardiac anomalies are associated with Tuberous Sclerosis?
Valvular obstruction due to rhabdomyomas.
What is an AV shunt?
An abnormal connection between an artery and a vein that bypasses the arterioles which is a major source of resistance.
What are the common physical exam findings in a patient with an AV fistula?
Pulsatile mass with a thrill on palpation. Auscultation reveals a constant bruit over the site
What alterations must be made to a drug regimen when prescribing both niacin and a hypertensive medication?
Niacin can potentiate the effects of some anti-hypertensive medications due to its vasodilatory effects.
What hemodynamic findings are associated with cardiac tamponade?
Pulsus paradoxus and arterial hypotension
What is pulsus paradoxus?
An exaggeration of the normal physiologic decrease in blood pressure that occurs during inspiration. It is defined as a drop in arterial blood pressure during inspiration of over 10 mmHg.
How can pulsus paradoxus be seen on physical exam?
By palpating the radial pulse and noting that it disappears during inspiration.
What condition is associated with pulsus parvus et tardus?
Aortic stenosis.
In a patient with severe aortic stenosis, why is a-fib so dangerous?
Because they often must rely on their L atrium for adequate LV filling due to concentric LV hypertrophy . Without this, LV preload can be drastically reduced.
What ion accumulations are characteristic of ion pump failure due to ATP deficiency during cardiac ischemia?
Intracellular accumulation of Na and Ca. These solutes draw in free water, causing cellular and mitochondrial swelling.
Endothelial damage due to atherosclerotic plaques attracts what cellular mediators to the site of damage?
First leukocytes; then platelets which release growth factors and cytokines
What is the function of PDGF in atherosclerotic plaque formation?
It is released locally by adherent platelets, endothelial cells, and macrophages and promotes migration of smooth muscle cells from the media into the intima and their subsequent proliferation.
What is seen on light microscope 4-12 hrs after MI?
Early coagulation necrosis, edema, hemorrhage, wavy fibers.
What is seen on light microscope 12-24 hours after MI?
Coagulation necrosis and marginal contraction band necrosis.
What is seen on light microscope 1-5 days after MI?
Coagulation necrosis and neutrophilic infiltrate.
What is seen on light microscope 5-10 days after MI?
Macrophage phagocytosis of dead cells.
What is seen on light microscope 10-14 days after MI?
Granulation tissue and neovascularization.
What is seen on light microscope 2 weeks to 2 months after MI?
Collagen deposition/ scar formation.
What class of drugs increases systolic and diastolic blood pressure while decreasing heart rate?
Selective a1 agonists (phenylephrine, methoxamine, etc). These drugs cause vasoconstriction and increased bp which stimulates baroreceptors in the carotid sinus and aortic arch to cause HR to slow. It reduces the SA node pacemaker activity and slows conduction.
What is Beck’s triad?
Hypotension, distended neck veins, and distant or muffled heart sounds (with tachycardia). It is characteristic of tamponade.
What is the mechanism of action of Dobutamine and what class of drugs does it belong to?
Beta adrenergic agonist with activity on B1 receptors and some B2 and a1 activity. It is a positive inotrope, has weakly positive chronotropic action, and increases cardiac conduction velocity. It also causes increased myocardial oxygen consumption.
What is dobutamine used to treat?
Acute heart failure associated with decreased myocardial contractility (i.e. cardiogenic shock).
What is myocardial hibernation?
A chronic, but reversible loss of contractile function secondary to persistent hypoperfusion of myocytes.
What is ventricular remodeling?
Involves chronic changes in mass, volume, shape, and myocyte composition of the heart to compensate for an increased hemodynamic load.
What is norepinephrine extravasation?
a1 receptor mediated vasoconstriction which can lead to local tissue necrosis secondary to NE infusion. The vein will become blanched, and induration an pallor of the tissues surrounding the IV will be seen.
How is tissue necrosis due to norepinephrine extravasation prevented?
By local injection of an a1 blocking drug such as phentolamine.
What EKG changes are seen in a patient taking beta blockers?
Prolonged PR interval due to slowed conduction through the AV node.
Which nitrate drug has the greatest bioavailability when taken orally?
Isosorbide mononitrate has almost 100% bioavailability.
On XRay, how does left ventricular failure present?
Cardiomeagly, vascular shadowing in a peri-hilar pattern (alveolar edema), blunting of the costophrenic angles (pleural effusions).
What are Kerley B lines?
Short horizontal lines perpendicular to the pleural surface that represents edema of the interlobular septa.
What condition is characterized by a genetic deficiency in lipoprotein lipase (LPL)?
Familial chylomicronemia syndrome (type 1 hyperlipoproteinemia)
How do patients with familial chylomicronemia syndrome present in childhood?
Marked hypertriglyceridemia, recurrent acute pancreatitis, lipemia retinalis (milky appearing vasculature), and eruptive xanthomas. These patients are not usually at increased risk for premature coronary artery disease.
What types of receptors does atenolol act on?
B1 selective antagonist
Where are B1 receptors found?
Cardiac tissue and renal juxtaglomerular cells
What is the progression of strawberry hemangiomas?
First they grow in proportion to the growth of the child before eventually regressing.
Describe the vascular reaction to endothelial and intimal injury.
Intimal hyperplasia and fibrosis, predominantly mediated by reactive smooth muscle cells that migrate from the media to the intima.
A mid systolic click followed by a murmur during the remainder of systole is characteristic of what condition?
Mitral valve prolapse.
What is the most frequent cause of mitral valve prolapse?
Defects in the mitral valve connective tissue proteins that predispose to myxomatous degeneration. This causes stretching and elongation of the valve leaflets and chordae tendineae by chronic hemodynamic stress.
During cardiac catheterization what hemodynamic finding is characteristic of mitral regurgitation?
An abnormally prominent upsloping atrial v wave.
What congenital malformations of the heart are associated with Turner’s syndrome?
Bicuspid aortic valve, coarctation of the aorta.
How would a non stenotic bicuspid aortic valve present on auscultation?
As an early systolic, high frequency click over the cardiac apex and/or right second interspace.
Rank the sodium channel binding strength of Class IA, B, and C antiarrythmatics.
1C> 1A> 1B. Thus use dependence is more pronounced in class 1c antiarrythmatics.
Quick dissociation from sodium channels has what effect on use dependence?
Minimal use dependence.
Which class of antiarrythmatics is most selective for ischemic cardiac tissue?
Class IB
What is the most common cause of fatigue and new onset cardiac murmur in a young adult?
Bacterial endocarditis. These symptoms may be complicated by acute diffuse proliferative glomerulonephritis secondary to circulating immune complexes and their mesangial and/or subepithelial deposition in the glomeruli.
What type of drugs is used to prevent reflex tachycardia caused by nitrates?
Beta blockers. They will slow conduction through the AV node and will decrease myocardial O2 demand.
To what class of drug does Dofetilide belong?
Class III K+ blocking antiarrythmic agent. It slows potassium efflux from the cardiac myocyte, affecting phase 3 of the action potential.
What drugs are considered first line treatment of isolated systolic hypertension?
Thiazide diuretics and dihydropyridine calcium antagonists in non diabetic patients (ACE-Is or ARBs would be first line in DM)
Name two common side effects of amlodipine.
Flushing and peripheral edema.
Dystrophic calcification is a hallmark of what cellular process?
Cell injury and death/ necrosis. It occurs in all types of necrotic tissue. This commonly occurs in aged or damaged cardiac valves.
On which receptors does NE act?
a1 and b1 receptors with minimal b2 adrenergic action. (a1= vasoconstriction; b2= vasodilation)
Phenoxybenzamine belongs to what drug class?
Nonselective, irreversible a1 and a2 receptor antagonist. It reduces the number of receptors available for NE binding.
What is the major clinical use of phenoxybenzamine?
Pheochromocytoma.
What drug class does Phentolamine belong to?
Reversible, competitive nonspecific a-adrenergic antagonist used in chatacholamine induced hypertensive crises (i.e. Pheo, MAOI crisis, cocaine overdose). High does of NE can overcome these effects.
How does severity of mitral stenosis affect the A2-opening snap interval?
More severe= shorter A2-OS interval.
Coarctation of the aorta may be associated with what vascular abnormalities?
Berry aneurysms of the circle of willis as well as aortic arch hypertension.
What abnormality is most likely to cause subsequent native valve bacterial endocarditis (NVBE)?
Mitral valve prolapse
What causes genetic cases of QT prolongation?
Mutations in the genes coding for cardiac cell potassium or sodium channels.
Name the most prominent inherited prolonged QT syndrome and the most common associated condition.
Jervell and Lange-Nielsen syndrome; neurosensory deafness.
What compensatory mechanism is used to prevent emboli when an atherosclerotic occlusion of a coronary artery develops slowly?
Development of collateral arteries around the point of occlusion.
Name three factors that destabilize plaques.
Thin fibrous cap, rich lipid core, active inflammation in the atheroma.
Episodic and transient anginal chest pain, occuring during the nightime hours accompanied by temporary ST segment elevations are characteristic of what condition?
Prinzmetal’s (variant )angina
What test is used to detect coronary vasospasm?
Ergovine stimulation test- it constricts vascular smooth muscle by stimulating alpha and serotonergic receptors.
How is Prinzmetal’s angina treated?
Vasodilating nitrates and CCBs
What drug significantly decreases heart failure progression as well as all cause mortality in patients with CHF?
Beta blockers, especially carvedilol. They should not be initiated in patients with unstable heart failure however,
What receptors does carvedilol act on?
Nonspecific B1 and B2 antagonist with a1 antagonist properties also.
What is the difference between eccentric and concentric hypertrophy?
Concentric results in uniform thickening of the ventricle walls and narrowing of the ventricle cavity with outer dimensions remaining relatively unchanged (usually due to increased ventricular afterload- pressure related); Eccentric causes dilation of the ventricle with associated increase in chamber size. It is usually caused by volume overload.
What is the most common cause of in-hospital death due to MI?
LV failure/ cardiogenic shock. Most frequent complication of coronary artery fibrinolysis is systemic bleeding.
What type of drug is metoprolol and on what tissues does it act?
B1 selective antagonist; Acts on B1 receptors on cardiac tissue and on renal juxtaglomerular cells. It exerts cardiac effects and also blocks catecholamine-induced renin release by the kidney.
What anomalous connection between cardiac chambers is considered a variant of normal in an adult patient?
Patent foramen ovale. It is patent in 20-30% of adults. Any abnormality that increases right atrial pressure above left atrial pressure can produce a right to left shunt across the foramen ovale.
What condition is defined by a systolic bp of greater than 160 mmHg with a diastolic bp below 90?
Isolated systolic hypertension. It is found in approximately 20-30% of patients 80 or older.
What causes isolated systolic hypertension (ISH)?
Age related decreases in compliance of the aorta and its proximal branches. Many structural changes are present in this- atherosclerotic changes contribute.
How does rheumatic heart disease affect the mitral valve compared to infective endocarditis?
Almost all cases of mitral stenosis are caused by rheumatic heart disease while infective endocarditis of the mitral valve tends to result in destruction and regurgitation. Congenital heart defects are also rarely related to stenosis.
How do you best hear an S3 sounds?
In the left lateral decubitus position, over the apex of the heart with the bell of the stethoscope.
What causes a pathological S3 heart sound?
A sudden deceleration of entering blood into the ventricle as it reaches its elastic limit. This produces a reverberation of blood between the ventricular walls which is heard as a low frequency sound early in diastole. The S3 sound develops when there is an imbalance between the force with which blood is pushed into the ventricle and the ability of the ventricle to accommodate this blood flow.
Give three conditions which will cause a S3 sound.
- Forceful, rapid filling of a ventricle that has normal or elevated compliance; 2. normal or even decreased filling rates when ventricular compliance is low; 3. blood flowing into an overfilled ventricle with high end systolic volume.
What is indicated by an S4 heart sound?
Diastolic dysfunction; most commonly caused by LVH
A dialated cardiomyopathy is indicative of what kind of heart disease?
Systolic dysfunction.
Name two possible causes of dilated cardiomyopathy.
Ischemic heart disease or dilated cardiomyopathy caused by viral myocarditis, cardiotoxigenic substances, peripartum state, genetic mitochondrial or cytoskeletal defects.
How does glucagon act on cardiomyocytes?
It activates G protein coupled receptors on cardiac myocytes causing activation of adeylate cyclase and raising intracellular cAMP. This causes increased calcium release from intracellular stores and increased SA node firing.
ACE-Is are inhibited in patients with what condition?
Bilateral renal artery stenosis and unilateral stenosis in a single functioning kidney.
Why are patients with renal artery stenosis dependent on ACE?
Need efferent arteriole constriction to maintain renal perfusion and GFR.
Direct arteriolar vasodilators have what systemic countereffect?
Significant arteriolar vasodilation causes reflex sympathetic activation and thus tachycardia and edema due to sodium and fluid retention.
What types of drugs are commonly administered with arteriolar vasodilators and why?
Sympatholytics and diuretics; counteract sympathetic effects of vasodilators.
Name two arteriolar vasodilation drugs.
Hydralazine, minoxidil
What are the early biochemical consequences of total myocardial ischemia?
Cessation of aerobic glycolysis and initation of anaerobic glycolysis. This transition occurs within seconds of ischemia. Loss of contractility occurs within 60 seconds of total ischemia.
In cardiac myocytes, ischemic injury becomes irreversible after how long?
About 30 minutes.
What drug both inhibits platelet aggregation and is a direct arterial vasodilator?
Cilostazol.
What is the mechanism of action of Cilostazol?
Phosphodiesterase inhibitor used in patients with intermittent claudication. It has also can be used to inhibit platelet aggregation and is a direct arterial vasodilator.
Which drug is superior to aspirin in the treatment of peripheral arterial disease?
Cliostazol.
Enlargement of the left atrium impinges on what nerve causing hoarseness?
Left recurrent laryngeal. This causes left vocal cord paresis.
What is Ortner syndrome?
Dilation of the left atrium sufficient to impinge on the left recurrent laryngeal nerve.
What vessels are most commonly involved in atherosclerosis?
Large elastic arteries- abdominal aorta, coronary arteries, popliteal arteries, internal carotids, circle of willis.
What are Aschoff bodies and in what condition are they typically found?
Interstitial collections of mononuclear inflammatory cells and scattered multinucleated giant cells surrounded by fibrosis of the interstitum. They are typically found in acute rheumatic carditis.
What are Anitschkow cells?
Plump macrophages with abundant cytoplasm and central, round to ovoid nuclei with central, slender chromatin ribbons. When the macrophages become multinucleated, they are called Aschoff giant cells.
On the level of tissue, describe the pathology of rheumatic heart disease.
Diffuse inflammation and aschoff bodies may present in any of the three layers of the heart; Aschoff bodies are later replaced by fibrous scar tissue.
What initates an aortic dissection?
A tear in the aortic intima that extends both proximally and distally and causes bisection of the aortic media.
What are class A vs class B aortic dissections?
A- dissections involving any part of the ascending aorta; B- confined to descending aorta.
What accounts for the blood pressure discrepency often seen in patients with aortic dissection?
Dissecting intramural hematoma spreads along the aortic wall compressing arterial branches. Sometimes, it may compress the brachiocephalic trunk.
What is the most serious complication associated with digoxin toxicity?
Life threatening ventricular arrhythmias.
The QRS complex corresponds to what phase of the ventricular myocyte action potential?
Phase 0.
What class of antiarrhythmics prolong the QRS but do not prolong the QT interval?
Class IC (ex. propaphone)
What cells express CD31?
PECAM1- platelet endothelial cell adhesion molecule
What is PECAM1?
A member of the immunoglobulin family of proteins that is expressed on the surface of endothelial cells and functions in leukocyte migration through the endothelium.
Hepatic angiosarcoma is associated with what exposures?
Carcinogens such as arsenic, thorotrast, polyvinyl chloride.
What cell marker is expressed by hepatic angiosarcoma cells?
CD31, an endothelial cell marker
In neonates, what is given to maintain a PDA and what is given to close it?
Indomethacin to close it, PGE1 to maintain it
Delayed closure of the ductus arteriosus is associated with what conditions?
Prematurity, perinatal distress, congenital rubella, fetal alcohol syndrome.
Acute onset heart failure in the setting of recent viral infection is associated with what pathology?
Dilated cardiomyopathy caused by viral myocarditis.
A high systolic pressure gradient between the left ventricle and aorta is indicative of what pathology?
Left ventricular outflow obstruction (i.e. aortic stenosis)
What characterizes dilated cardiomyopathy?
DIagnosis of exclusion- dilation of all four chambers, systolic dysfunction, myocardial failure.
What are fatty streaks?
Earliest lesions in the progression to atherosclerosis. They are composed of intimal lipid filled foam cells derived from macrophages and smooth muscle cells that have engulfed lipoprotein (LDL) which has entered the intima through an injured, leaky endothelium. They have a foamy appearance due to intracellular lipid containing phagolysosomes.
What cell types are the predominant constituents of fatty streaks?
Foam cells.
What characterizes unstable angina or subendocardial infarction?
An ulcerated atherosclerotic plaque with a partially obstructive thrombus
What characterizes a transmural MI?
An atherosclerotic plaque with a fully obstructive thrombus.
What characterizes stable angina?
Fixed atherosclerotic plaques occluding more than 75% of the coronary artery lumen.
What is Churg-Strauss Syndrome?
Idiopathic systemic vasculitis defined as the combination of adult-onset asthma, eosinophilia, history of allergy, mono-or polyneuropathy, migratory/transient pulmonary infiltrates, and paranasal sinus abnormalities.
What drug causes a dose dependent increase in cardiac contractility and a dose dependent decrease in systemic vascular resistance?
Isoprotenol- it increases cardiac contratility by acting on myocardial b1 adrenergic receptors but in lower doses it selectively binds b2 receptors which causes relaxation of vascular smooth muscle. It has no effects on alpha receptors.
A PDA murmur is best heard at what location?
Left infraclavicular region with maximal intensity at S2
Administration of what agents improves flushing associated with niacin?
Prostaglandins (i.e. 325 mg aspirin), nicotinic acid
How does capsaicin reduce pain?
By decreasing the level of substance P in the peripheral nervous system.
What class of drugs can be used to treat both benign prostatic hyperplasia and hypertension?
Alpha-1 blockers.
Name three alpha 1 blockers.
Doxazosin, Prazosin, Terazosin.
Patients with coronary artery disease and heart failure along with hypertension will benefit from what type of drug?
Cardioselective beta blockers.
What is the first line medication used for treatment of essential hypertension in the general population?
Hydrochlorothiazide.
How is HOCM inherited and what mutation is associated with this condition?
Autosomal dominant mutation in cardiac sarcomere proteins. Most common mutation is beta-myosin heavy chain.
What genetic mutation is associated with 1/3 of the cases of dilated cardiomyopathy and how is this inherited?
Autosomal dominant mutations of cardiac myocyte cytoskeletal proteins or mitochondrial enzymes.
Polyarteritis nodosa (PAN) affects what types of vessels?
Small to medium sized arteries in any organ- kidney, liver, heart, GI tract are most commonly involved. It typically spares the pulmonary arteries and the lungs.
How does polyarteritis nodosa manifest clinically?
Ischemia, infarction, hemorrhage of small to medium sized vessels and cutaneous manifestations including palpable purpura.
Insoluble pigment composed of lipid polymers and protein complexed phospholipids in myocardial cells are indicative of what condition?
Normal aging.
What are lipofuscin particles?
Yellow brown, finely granular perinuclear pigment which is the product of free radical injury and lipid peroxidation. It is commonly seen in the heart and liver of aging or cachectic malnourished patients.
What ionic imbalance causes QT prolongation?
Decreased outward K+ current during the repolarization phase of the cardiac action potential.
Where is prostacyclin produced?
From prostaglandin H2 by prostacyclin synthase in vascular endothelial cells.
What are the functions of prostacyclin?
When secreted, it vasodilates, inhibits platelet aggregation, and increases vascular permeability.
Which two factors oppose each other and work in concert to ensure vascular homeostasis?
Prostacyclin and thromboxane A2.
What is the function of Protein C in the coagulation cascade?
It inactivates factors Va and VIIIa.
Bacterial colonization of vegetations associated with bacterial endocarditis are formed on what sites?
On sites of fibrin and platelet deposition.
What is differential cyanosis and in what condition is it expressed?
Cyanosis of the lower extremities but not of the upper body. It is commonly present in patients with PDAs.
What is the difference between presentation of a patient with a PDA vs coarcation of the aorta?
No cyanosis in coarctation.
Describe the action of class III antiarrythmatics.
Slowed potassium efflux from the ventricular myocyte, prolonging repolarization and the refractory period.
Name four class III antiarrhythmatics.
Dofetilide, Sotalol, Ibutilide, Amiodarone.
What type of murmur is associated with aortic regurgitation?
Early diastolic murmur.
With increasing severity of aortic regurgitation, how does the murmur change?
More advanced cases produce a holosystolic murmur and more mild cases have only an early diastolic murmur.
What is the most common cause of aortic regurgitation in developed countries and where is this murmur best heard?
Aortic root dilation (Best heard at the right sternal border) or bicuspid aortic valve.
Name the two congenital syndromes of QT prolongation.
Romano-Ward syndrome and Jervell and Lange Nielsen syndrome.
From what artery does the sinus node receive its blood supply?
RCA.
What artery supplies the posterior inferior wall of the left ventricle?
RCA.
Transmural ischemia due to RCA occlusion shows what EKG changes?
ST elevation in leads II, III, and aVF as well as possible sinus node dysfunction.
Transmural ischemia due to LAD occlusion would show what EKG findings?
ST elevations in V1-V4 caused by anteroseptal transmuarl ischemia.
Occlusion of the LCX would produce what EKG changes?
Transmural ischemia of the lateral wall of the left ventricle with ST elevations in V5 and V6 and possibley in I and aVL.
In patients with hypertension and chronic ischemic myocardial failure, what class of drugs is considered first line and why?
ACE-Is- they inhibit cardiac remodeling and the associated deterioration of ventricular contractile function in addition to reducing blood pressure. Beta blockers would also be useful.
