exported flash cards
acute graft rejection findings on histology
dense interstitial lymphocytic infiltrate occurs weeks after transplant, cell mediated process, tx= preventative immunosuppr drugs
describe hyperacute rejection after transplant
acute cession of blood flow after joining the circulations, due to preformed ab to donor antigens
ischemic damage on histology
patchy necrosis with granulation tissues
chronic rejection of a transplant on histology
scant inflammatory cells and interstitial fibrosis T cell and B cell mediated (ab mediated too)occurs months to years after a solid organ transplant
Interstitial myocardial granulomas (aschoff bodies) are characteristic of what?
(look up a picture)
carditis due to acute rheumatic fever…. s/p untreated group A strep pharyngeal infection
anschoff bodies= plump macrophages with abundant cytoplasm and central slender ribbons of chromatin (anitschkow/caterpillar cells)
ARF = type 2 HSR PSGN = type 3
immune mediated complication is PSGN, biggest problem is pancarditis/mitral valve regurg (holosystolic murmur)
over subsequent years, anschoff bodies are replaced by fibrous scar tissue leading to chronic mitral valve stenosis and regurg
what are the cardiotoxic chemo agents and what do you see on histology
anthracyclines (doxorubicin and daunorubicin)
cause dose related acute and chronic cardiac damage (dilated cardiomyopathy)
biopsy= patchy fibrosis with vascuolization and lysis of myocytes
what mutation causes hypertrophic cardiomyopathy (HOCM)?
mutation of sarcomere genes
leads to left ventricle hypertrophy, systolic and diastolic dysfunction
histology= disorganized hypertrophied myocytes
Chagas disease is caused by what and looks like what?
Recent travel to South America and infection by the protozoan parasite Trypanosoma cruzi
results in myocarditis= distension of individual myofibers with intracellular trypanosomes
viral myocarditis appearance on histology
lymphocytic infiltrate with focal necrosis of myocytes
no anschoff bodies
causes= adenovirus, coxsackie B virus, parvovirus B19
Patient with hx of MVP just had a dental cleaning and is now infected with a gram pos bacteria that synthesized dextrans from sucrose
This is strep viridans and the patient now has transient bacteremia
MVP= systolic click and murmur
strep viridans make dextrans (extracellular polysacch) with sucrose as substrate. dextrans help the strep adhere to fibrin-platelet aggregates (because these get deposited at sites of endothelial trauma which is where viridans gets it’s entrance)
risk of endocarditis is still low for dental work with MVP so you dont need abx prophylaxis
how does heparin work?
activate anti-thrombin 3 to decrease thrombin activity and prevent fibrinogen from converting to fibrin (thus preventing clot formation and prolonging the PTT)
Embryology behind tetralogy of Fallot (TOF)?
caused by the deviation (anterior and cephalad) of the infundibular septum (due to abnormal neural crest cell migration)= resulting in a malaligned VSD and overriding aorta
presentation= cyanotic spells that improve with squatting, prominent right ventricular impulse, systolic murmur
4 abnormalitis:
- VSD
- overriding aorta over the right and left ventricles
- RVOT obstruction (ex= pulm stenosis or narrowing)
- RV hypertrophy
cyanosis is the right to left shunt caused when RVOT obstruction worsens (causes a harsh systolic ejection murmur…crescendo decrescendo… ofer the mid to left upper sternal border
squatting= increases afterload and decreases the degree of right to left shunt across the VSD
what is TAPVR?
Total anomalous pulmonary venous return= all 4 of the pulmonary veins drain abnormally into the right atrium (with an obligatory right to left shunt)
leads to right atrial and ventricular dilation
Describe coarctation of the aorta
aortic arch constriction commonly located distal to the left subclavian artery (juxtaductal)
you get a brachial femoral pulse delay and BP discrepancy between the upper and lower extremities
Common in turner syndrome
embryology behind defects of the atrioventricular septum and valves (ie- mitral and tricuspid valves)
Failed fusion of the superior and inferior endocardial cusions
show up as atrial defects or VSD with left to right shunt
Over time leads to Eisenmenger syndrome (pulm HTN causes reversal of the shunt)
embryology of transposition of the great arteries
from linear development of the aorticopulmonary septum (instead of the normal spiral)
Describe the EKG findings of atrial fibrillation with rapid ventricular response
ABSENT P WAVES, irregularly irregular R-R intervals, narrow QRS complexes, fibrillatory waves (chaotic continuous atrial depolarizations due to creation and persistence of multiple ectopic foci and reentrant impulses in the atria…aka independent of SA node)
ventricular contraction rate in Afib with RVR is determined by the AV node refractory period, hence most of the atrial impulses never reach the ventricles
Bundle branch conductivity’s affect on ventricular contraction
none. bundle branch conductivity determines the duration of the QRS complexes (QRS widens when there is a block)
When does the purkinje system assume pacemaker activity in the heart?
in patients with severe bradycardia (<40 bpm)
how does the ventricular muscle refractory period affect contraction rate of the heart?
the ventricle’s refractory period does not limit contraction rate because it can approach 300 bpm in ventricular tachycardia
Describe heterozygous familial hypercholesterolemia
Aut Dom LDL receptor defect causing high LDL levels and increasing the risk of premature atherosclerosis
What is southern blotting used for
detect DNA mutations
extract DNA from cells, break it into fragments with a restriction endonuclease, separate the fragments by size using gel electrophoresis, and identify the gene target using a DNA probe (a single strand portion of labeled DNA complementary to the gene of interest)
a new test for MI has a sensitivity of 75% and specificity of 80%. 600 patients are enrolled and 200 are confirmed to have MI. How many false negatives are expected?
50
the sensitivity measures the true positives and the false positives.
a true positive is complementary to false negative (the total of TP + FN always= number of confirmed patients)
Thus if the sensitivity of the test is 75% then the test will correctly identify 75% of the confirmed 200 (which is 150)…. meaning that 25% of the patients are false negatives (which is 50)
describe a cardiac pacemaker action potential
sodium= phase 4 slow upstroke, “funny current”
calcium= phase 0 rapid upstroke
potassium= phase 3 repolarization
ex= SA node
exhibit automaticity (depolarize without external influences),
Describe the AP of a non cardiac pacemaker cell
sodium= phase 0 rapid vertical upstroke
potassium= tip/point of the AP, aka phase 1= early short replarization (K out and decreased Na conductance)
calcium= phase 2, the horizontal delay before repolarization (inward Ca counteracts K out)
potassium= phase 3 repolarization
resting membrane potential (-90mV)= phase 4, flat line horizontal… near equalibrium potential of potassium
in cardiomyoctes and purkinje cells
How does adenosine and dipyridamole work to cause ischemia?
adenosine and dipyridamole are vasodilators selective for coronary vessels
Basically when there is ischemia (chronic due to atherosclerosis), collateral vessels are made to keep the heart perfused.
Then these drugs come in and vasodilate the heart, BUT the ischemic areas are already maximally dilated, so dilation of the normal (coronary arterioles) vessels steals blood from the ischemic areas and exacerbates the myocardial ischemia… “coronary steal”
Adenosine and dipyridamole use this principle in perfusion imaging studies during exercise to detect areas of ischemia not otherwise seen in the resting heart
Describe NSAID effects on the kidney
Prostaglandins dilate the afferent arteriole (before the glomerulus), which increases GFR by bringing in more blood flow relative to the efferent arteriole
blocking prostaglandins with NSAIDS blocks this affect
Describe ACEI effects on the kidney
angiotensin 2 causes constriction of the efferent arteriole which increases GFR by having more blood flow come in relative to the smaller size of the efferent arteriole
ACEI blocks this affect
angiotensin 2 also increases aldosterone so ACEI block this increase and hold onto potassium
what is an EKG finding of chronic digoxin use
shortened ST segments and the scooped out appearance of the ST segment
name two drugs for acute heart failure
milrinone (phosphodiesterase inhibitor that inhibits the breakdown of cAMP which increases contractility and vasodilation)
and nesiritide (synthetic BNP, increases cGMP, vasodilation, and natriuresis)
what does vagus nerve stimulation do to the heart
vagus nerve stimulation increases parasympathetic effects on the heart (and is why digoxin can act as an antiarrhythmia drug to slow down the SA and AV nodes)
what are symptoms of digoxin toxicity
nausea, vomiting, abdominal pain, and YELLOW VISION (xanthopsia)
hypokalemia exacerbates toxicity. renal problems and other drugs can impair excretion.
digoxin with a very narrow theraputic index
true or false: ACEI are protective of diabetic nephropathy
True. Indicated in DM patients with albuminuria or in DM with hypertension to prevent progression of kidney disease!
cardiac tamponade symptoms
hypotension
tachycardia
jugular venous distension (with clear lungs)
pulsus paradoxus (loss of palpable pulse during inspiration… >10 mmHg decrease in systolic BP because inspiration increases blood flow to the right heart but when the heart’s expansion is impaired the increased RV volume causes the interventricular
septum to bow into the LV which decreases LV end diastolic volume and stroke volume causing systolic pressure to drop)
causes include recent viral illness causing a viral pericarditis with significant pericardial fluid accumulation (due to inflammation)
does inspiration increase or decrease blood volume to the heart?
increase
increases venous return
cardiogenic shock symptoms
hypotension
tachycardia
jugular venous distension
pulmonary edema
pulsus paradoxus not seen
causes of pulsus paradoxus
cardiac tamponade
asthma
COPD
constrictive pericarditis
tension pneumothorax symptoms
breath sounds absent on affected side
hyperresonance (too much air) to percussion on affected side
tachypnea
tachycardia
hypotension
distended neck veins
tracheal deviation to the contralateral side
Name the pharyngeal arches and what theyre associated with
each arch has a cranial nerve and an aortic arch
1st arch= first aortic arch (regresses except for maxillary artery) and trigeminal nerve
2nd arch= second aortic arch (regresses) and facial nerve (muscles of facial expression, some ear and hyoid associated structures)
3rd arch= common and proximal internal carotid arteries (inward of sternocleidomastoid muscle) and glossopharyngeal nerve… also the hyoid bone and stylopharyngeus muscle
4th arch= true aortic arch and subclavian arteries, superior laryngeal branch of the vagus nerve… also muscles of pharynx and soft palate and some laryngeal muscles
5th arch= obliterated during fetal development
6th arch= pulmonary arteries and ductus arteriosus, recurrent laryngeal branches of the vagus nerve
Describe hyperhomocysteinemia
elevations in pasma homocysteine due to genetic mutations in critical enzymes and vitamin (cofactor) deficiencies
most common genetic cause= MTHFR def… TetraHydroFolate Reductase regenerates methyl tetrahydrofolate with FAD as a cofactor
(also low vit B’s- cobalamin B12, pyridoxine B6, folate B9)… supp with vit B not shown to help CV risk or mortality
high plasma homocysteine= independent clot risk (due to endothelial damage)
homocysteine —-(remethylation via methionine synthase using methyl THF + B12)——> methionine
homocysteine —–(transsulfuration)—–> cystathionine —– (cystathionase + B6) —-> cysteine
homocysteinemia due to MTHFR mutation impairs production of what
methionine
Patient with hypertensive heart failure given nitroprusside infusion. How does his cardiac pressure volume cycle change?
Nitroprusside is a short acting balanced venous and arterial vasodilator
thus it will decrease preload and afterload (to the LV)
decrease in preload (LVEDP)= shifts the whole cycle to the left towards lower volumes (preload is specifically the right-most line on the cycle)
decrease in afterload (mean systolic intraventricular pressure)= squishes the cycle down vertically from the top (with the top line=afterload reflecting lower pressure)
No change in stroke volume (the width of the cycle)
What is alteplase (and tenecteplase)?
fibrinolytic= binds fibrin in the clot and converts the entrapped plasminogen into plasmin (which lyses the clot by hydrolyzing fibrin matrix bonds)
given to achieve myocardial reperfusion for acute MI within 12 hours of onset (percutaneous coronary intervention is preferred because it has lower rates of intracerebral hemorrhage and recurrent MI)
symptoms of intracerebral hemorrhage
abrupt decreased LOC (comatose)
asymmetric pupils
irregular breathing
most common ADR of fibrinolytic therapy is hemorrhage
symptoms of thrombus causing stroke
causes an ischemic stroke with fluctuating symptoms and may have periods of improvement
symptoms of aortic dissection
severe tearing chest pain radiating between the scapula
common in HTN patients or marfan(fibrillin mut)/ehlers (collagen mut) danlos syndrome patients
CXR with widened mediastinum
symptoms of reperfusion injury
results in paradoxical cardiomyocyte dysfunction
Basically: arrythmias
myocardial stunning (prolonged but reversible contractile dysfunction)
myocyte death
what are contraindications for treatment with fibrinolytics
GI bleed
recent surgery
What is the SVC derived from
The common cardinal veins
embryonic development has three vein origins:
- umbilical (degenerates)
- vitelline (form the portal system)
- cardinal veins (systemic venous circulation)
What is “holiday heart syndrome”
Atrial fibrillation seen in patients after excessive alcohol consumption
(otherwise healthy patient, usually temporary)
what does a prolonged QT interval put you at risk for
torsades de pointes (polymorphic ventricular tachycardia)… and sudden death
can be congenital or acquired (chronic heavy alcohol use)
Double blinding of a study prevents what bias?
observer bias
what is beta error?
concluding there is no different when one actually exists
it is a random error not a systematic error/bias
what cell type is involved in the first step of atherosclerosis?
endothelial cells
atherosclerosis is initiated by repetitive endothelial cell injury leading to chronic inflammatory state underlying the intima of large elastic arteries and medium/large muscular arteries
repetitive injury from: HTN hyperlipidemia smoking DM homocysteine toxins (alcohol) viruses immune reactions ..... these expose subendothelial collagen or cause endothelial cell dysfunction
endothelial cell dysfunction leads to increased permeability, monocyte and lymphocyte migration into the intima, platelet adhesion (denudation and exposure of the subendothelial collagen), smooth muscle cells migrate into the intima and proliferate (due to growth factors released by monocytes and platelets), LDL cholesterol gets into the intima due to permeability, macrophages take up LDL to produce foam cells, SMCs deposit the LDL and produce more extracellular matrix (collagen and proteoglycans), this leads to fatty streaks (lipid laden foam cells), this leads to a fibrofatty atheroma—–> atherosclerosis
fibrous cap of an atherosclerotic plaque (atheroma) is made of what
SMCs that have migrated to and proliferated in the intimal layer in which plaque forms
What does strep gallolyticus (formerly S bovis) cause?
the main pathogen in the non-enterococcal group D strep family
it causes subacute bacterial endocarditis (without pre-existing valvular abnormality) with symptoms similar to S viridans
its a normal part of the colon flora… when it causes bacteremia or endocarditis then 25% of the time the strep gallolyticus is associated with colonic cancer
when a blood culture grows strep gallolyticus you should do a colonoscopy!
What bacteria commonly causes right sided endocarditis in IV drug users
staph aureus
what bacteria causes SBE following dental work?
strep viridans
What is aliskiren?
a direct renin inhibitor
can cause hyperkalemia due to decreased aldosterone levels
what type of calcium channels are in the heart and smooth muscle of the vasculature?
L type calcium channels in heart and smooth muscle
smooth muscle calcium channels blocked by dihydropyridines (-dipine suffix)
non dihydropyridines are block cardiac calcium channels (verapamil, diltiazem)… contractility and decreased activity of SA and AV nodes
nifedipine (a short acting dihydropyridine- CCB) can exacerbated MI how?
due to reflex tachycardia
Thus it is contraindicated in patient’s with unstable angina or MI
all CCBs can worsen heart failure
Name two drug types off sketchy that are used in hypertensive emergency
- Potent vasodilators (hypotension leads to reflex tachycardia/SNS activation and increased renin levels=ADRs)
- IV CCBs (dihydropyridines)
- hydralazine (safe for pregos, arterial vasodilator only)… add BB or nitrate for reflex tachycardia… can cause drug induced lupus
- nitroprusside (a nitrate, systemic vasodilation via NO-increase cGMP=smooth muscle relaxation).. problem=metabolized to cyanide—> lactic acidosis/seizures
- fenoldopam (DA 1 receptor antag= increased cAMP= arterial vasodilation, esp renal a. and coronary a… also causes natriuresis) - IV beta blocker (esmolol, metoprolol- anti beta 1…. labetalol- anti alpha and beta)… can be added to help minimize reflex tachycardia of the vasodilators
What are the first line drugs for HTN
- Thiazides (chlorthalidone may be better)
- ACEI/ARBs (with HF, MI, DM)
- CCBs (good for African Americans and elderly…dihydropyridines)
(and beta blockers I think)
if BP >20/10 then combine two antihypertensives
What blood pressures indicate hypertensive emergency?
systolic above 180
diastolic above 120
what are symptoms of hypertensive emergency?
HTN >180/120 blurry vision headache lung crackles neuro symptoms (end organ damage symptoms here)
why is it important to reduce blood pressure slowly in a HTN emergency?
To prevent ischemia
lower by 10-20% in the first hour
then 5-15% in next 23 hours
what does the murmur of a VSD sound like?
turbulent flow across a small VSD makes a loud holosystolic murmur best heart over the left lower sternal border
(may be absent if the VSD is large because there is less resistance)
VSD= failure of PROLIFERATION of endocardial cushions (normally forming the membranous part of the interventricular septum)
Describe the murmur of HOCM
A bifid carotid pulse with a brisk upstroke (“spike and dome”)…. remember LVOT obstruction during systole
also thought of as a systolic crescendo-descrescendo murmur
what does the murmur of a patent ductus arteriosus sound like
precordial, continuous machine like murmur
pulm a. will have elevated SpO2
why does an ASD cause fixed splitting of S2
because equalization of the left and right atrial pressure minimizes the respiratory variation in ventricular blood flow
mucosal cyanosis and fingernail clubbing can indicate what cardiac issues?
cyanotic congenital heart disease or late features of ASD/VSD (due to Eisenmenger syndrome)
Describe the adverse reactions of arteriolar vasodilators
selective arteriolar vasodilators (hydralazine, minoxidil) reduce vasc resistance but cause a reflex SNS activation because baroreceptors get activated
SNS= increase HR/contractility/CO and simulation of RAAS (sodium and fluid retention leading to tachycardia and peripheral edema….these offset the BP lowering effect and limit the long term use)… the SNS activation here does not raise BP above baseline unless stopped abruptly
in resistant hypertension you can add on a sympatholytic or diuretic to combat these ADRs
name some ADRs of ACEIs
persistent dry bradykinin cough and angioedema (localized to subcutaneous or submucosal unlike peripheral edema)
describe the effect of certain foods on MAO inhibitors
MAO inhibitors (tranylcypromine, phenelzine) increase synaptic monoamine levels by inhibiting monoamine degredation in order to treat atypical or resistant depression
MAOi also block degredation of dietary tyramine (indirect sympathomimetic), allowing it to enter systemic circulation and cause SNS hyperactivity and HTN emergency
dietary tyramine= aged cheeses, cured meats, draft beer (“fancy meats and cheeses”)
How to TCAs work?
antidepressants that inhibit reuptake of monoamines (norepi and serotonin)
imipramine, amitriptyline, clomipramine
How does bupropion work?
presynaptic selective dopamine and norepi reuptake inhibitor
treats major depression and tobacco dependence
ADRs= seizures
contraindicated in bulimia or anorexia patients
The catalase test with 3% hydrogen peroxide differentiates which bacterias
staph (+) from strep (-)
The ability to clot blood plasma (slide and tube coagulase tests) separates what bacteria into what groups
separates staph into positive and negative groups
positive= staph aureus (ferments mannitol, yellow pigment)… endocarditis of IV drug abusers and most common cause of osteomyelitis
negative= staph epidermidis (novobiocin susceptible)/haemolyticus/saprophyticus (novobiocin resistance)/etc
staph epidermidis is a skin contaminant that can cause an opportunistic infection including endocarditis to prosthetic valves and septic arthritis to prosthetic joints
Describe the murmur of a PDA
continuous machine like murmur appreciated between the scapulae
Describe the presentation of TGA (transposition of the great arteries)
incompatible with life unless there is a coexisting connection like a patent foramen ovale, septal defect, or PDA to allow oxygenated blood to mix with systemic circulation
patient normal on initial presentation but as the PDA closes around 1-3 days old they get cyanotic, tachypneic, and tachycardic (elevated lactate as a consequence of anaerobic metabolism in the presence of poorly oxygenated blood)
etiology of TGA= failure of normal spiraling of the aorticopulmonary septum in utero (thus aorta is anterior and inferior implying its connection off of the RV and pulmonary artery connection to LV)… basically you get two parallel circulations without communication when the PDA closes
hypospadias is an embryogenic failure of what?
failure of FUSION of the urethral folds to fuse
what is the cause of a branchial cleft cyst
failure of OBLITERATION of the second branchial cleft
the cyst usually present as a draining sinus at the angle of the mandible
What causes truncus arteriosus?
failure of conotruncal SEPTATION
presents with cyanosis and respiratory distress
echo shows a large single arterial trunk and overriding large VSD
What is the most common cause and sequelae of infective endocarditis in an IV drug user
Staph aureus causes infective endocarditis in IV drug users resulting in tricuspid regurg
Tricuspid regurg= early systolic murmur best heard in tricuspid area accentuated by inspiration (because inspiration increases blood flow to the right heart)
On a cardiac pressure volume loop what does the right most vertical line and top most horizontal line mean
The right most vertical line= preload
The top most vertical line= afterload
What would increased contractility look like on a cardiac pressure volume loop?
higher pressures would be reached during ejection phase and a greater volume of blood would be ejected during contraction (loop would get wider)
ex= infusion of dobutamine
What test should be used to compare the means of two groups?
a two sample t test
When should linear regression be used?
to model the linear relationship between a dependent variable and an independent variable
described in terms of a trend line
ex= number of cigarettes smoked per day and the number of yearly hospitalizations in COPD patients
what is the difference between linear regression and correlation coefficient?
linear regression is a single number that is reported to describe the strength and magnitude of the association (ex= number of cigarettes smoked per day and the number of yearly hospitalizations in COPD patients)
correlation coefficient is a measure of strength and direction of a linear relationship
(ex= correlation coefficient describing the association between estrogen and breast cancer risk in post menopausal women)
basically it seems that correlation coefficient compares things that are more closely linked
When to use a chi square test
with categorical data
evaluate whether the expected frequency of an occurrence is consistent with the observed frequency (“goodness of fit”)
what test compares the means in 3+ groups?
ANOVA
What is a meta analysis?
epidemiologic method of analyzing pooled data from several studies, therby increasing the statistical power beyond the individual study
Describe ARBs
Angiotensin 2 receptor blockers (-sartans) competitively bind and block the effects of angiotensin 2 resulting in vascular smooth muscle relaxation and decreased aldosterone secretion
because this decreases BP, renin levels increase (and thus also increases angiotensin 1 and 2)….answer was ARB= increase in renin, angiotensin 1 and 2, decrease in aldo, no change in bradykinin
bradykinin levels are unaffected cause ACE is left alone in the lungs
what affect does a beta blocker have on RAAS?
beta 1 blockers would inhibit renin release and thus supress the entire RAAS cascade (somewhat blunted by the lowered BP)
What are the hemodynamic actions of epinephrine and what receptors mediate those responses
Epi: beta1=beta2>alpha1
increases HR and contractility (via beta 1)
increases systolic BP (via beta 1 and alpha 1)
low dose epi decreases diastolic BP (because beta2>alpha1)… beta 2 is vasodilation
high dose epi increases diastolic BP (alpha1>beta2)
Name a nonselective beta antagonist
propranolol
Name a nonselective beta agonist
isoproterenol
Name a nonselective alpha blocker
phentolamine
Name a selective alpha agonist
phenylephrine
Describe the acute and chronic changes seen due to an arteriovenous fistula
acute= decrease in TPR resulting in increased CO and venous return.
chronic= SNS and kidneys compensate for the chronic fistula by increasing cardiac contractility, vascular tone, and circulating blood volume… also increase the mean systemic pressure
Describe acute rheumatic fever’s effect on the heart
almost always affects the mitral valve
affects mitral and aortic valves in 25% of the cases (combined aortic stenosis and regurg which can predispose to infective endocarditis)
infective endocarditis from ARF can cause embolization causing stroke (one sided hemiparesis) due to embolism from either clot formed during atrial dilation (from mitral stenosis) or endocarditis related valvular vegitation
what are fatty streaks made of?
collections of lipid laden macrophages (foam cells)
Describe the findings of wolf parkinson white syndrome (WPW syndrome)
it is due to an atrioventricular conduction tract bypassing the AV node (an atrioventricular accessory pathway)
in WPW there is an extra conduction pathway (called the accessory bypass tract or bundle of kent) directly connecting the atria to the ventricles allowing for pre excitation of the ventricles
characteristic EKG triad:
- short PR interval
- widened QRS
- slurred broad upstroke of the QRS complex (delta wave)
WPW also associated with AV reentrant tachycardia
what syndrome do you see delta waves on EKG
Wolf Parkinson White Syndrome
delta wave looks like a bunch of peaked t waves but the upstroke of the QRS complex is slanted and not vertical
What are the main ADRs of nitrate therapy
headaches cutaneous flushing light headedness hypotension reflex tachycardia
avoid in patients with HOCM, RV infarction, and who are also on phosphodiesterase inhibitors (synergistic affect)
Restrictive cardiomyopathy (diastolic heart failure) causes
idiopathic
infiltrative disease caused (amyloidosis, sarcoidosis, hemochromatosis)
radiation fibrosis
endomyocardial fibrosis
The infiltrative causes lead to significant ventricular hypertrophy
cardiac amyloidosis [amorphous and acellular pink material=amyloid... congo red stain shows apple green birefringence under polarized light microscopy] results from abnormal extracellular deposition of insoluble proteins such as: monoclonal light chains (AL amyloidosis) mutated transthyretin (familial ATTR amyloidosis) wild type transthyretin (senile systemic amyloidosis)
What is a cardiac myxoma
cardiac myxomas are the most common primary cardiac neoplasm with 80% being in the LA
symptoms= syncope and heart failure
histo= numerous bland stellate cells in a background of myxoid ground substance
what is cardiac sarcoidosis
presents with restrictive or dilated cardiomyopathy along with conduction defects and arrythmias (can cause sudden death)
histo= non caseating granulomas with giant cells
What is Chagas disease’s affect on the heart
trypanosoma cruzi infection causes myopericarditis and cardiomyopathy in Latin America
histo= multiple parasitic protozoa within the myocardial fibers with dense cellular infiltrate and myofiber destruction
hemochromatosis affect on the heart
excessive iron deposits in the myocardium causing conduction abnormalities and restrictive or dilated cardiomyopathy
histo= excessive iron deposition in the myocardium confirmed with prussian blue stain
which phase of the cardiac cycle is the myocardium perfused with blood
during diastole
(diastole duration shortened during increased HR) thus during exercise, diastole time decreases and becomes the major limiting factor for coronary blood supply
normally during exercise, flow mediated dilation and vasodilators (adenosine and NO) ensure adequate coronary blood supply
true or false: papillary muscle rupture leading to regurgitation is a complication of an acute MI that occurs 3-5 days later
true
mitral valve:
anterolateral papillary muscle= dual blood supply from LAD and left circumflex
posteromedial papillary muscle= blood supply from only the posterior descending artery (from right coronary artery in right dominant circulation or left circumflex in left dominant circulation)
What is the mechanism of class 1 anti-arrhythmic drugs?
Block sodium channels (by binding to open or inactivated sodium channels) to decrease the slope of phase 0 upstroke….
slowing the upstroke slows conduction of the AP through the tissue (this widens the QRS… QRS widens more with faster heart rates due to the use dependence)
“use dependence” this drug affects tissues with greater depolarization activity more
describe the three types of class 1 anti-arrhythmics
1A (1. quinidine-prom queen, causes cinchonism [tinnitus, HA, dizz] and thrombocytopenia 2. procainamide-prom king, lupus like syndrome [ANA ab increased] 3. disopiramide-"disappears", negative ionotrope)... also block k+ channels to prolong refractory period... use for WPW syndrome (SVT)... class 1A causes QT prolongation (precipitates torsades due to the K+ blocking)
1B (1. lidocaine- “LIED”, 2. phenytoin- “friendly towing”, anti-epileptic drug with some 1B properties 3. mexiletine- mexican flag)…
shorted phase 3 repolarization by blocking sodium channels during depolarization= shorten AP duration… more selective for tissues with sodium channels (ventricles and purkinje system rather than the atria because they have longer APs)= thus they treat ventricular arrhythmias (esp ischemic tissue)… most common ADRs of 1B= neuro [parasthesias, tremor, convulsions]
1C (1. flecainide- corn flakes, 2. propafenone- purple phone)…
No affect on k+ (no affect on AP duration)… good for atrial and ventricular arrhythmias… great for afib…
because of pro-arrhythmic affects, 1C is contraindicated in patients with structural heart problems or ischemic heart disease
Sodium channel binding strength(use dependence): 1C (strongest use dependence and slowest dissociation)> 1A>1B (least use dependence
most sensitive and specific marker for MI
Troponin I
rises 2-4 hours after infarction
peaks at 24 hours
normal by 7-10 days
best serum marker for detecting reinfarction after MI
CK-MB
rises 4-6 hours after infarction
peaks at 24 hours
normal by 72 hours
What is the treatment for acute MI?
Aspirin/heparin
supplemental O2
nitrates
beta blocker (prevent arrhythmia and decrease oxygen demand)
ACEI (prevent increase in LV volume/dilation)
Consequences of fibrinolysis or angioplasty (treatment of acute MI)
Contraction band necrosis (from calcium returning to cells upon reperfusion and causing contraction)
Reperfusion injury (via oxygen free radicals)
After an MI, describe the progression of healing on a tissue level using the intervals of 1 day, 1 week, and 1 month
MI
Coagulative necrosis [dark discoloration]
1 day
inflammation (neutrophils then macrophages) [yellow pallor]
1 week
granulation tissue [red border emerges as GT enters from edge of infarct]
1 month
scar [white scar]
What are the complications after an acute MI in relation to 1 day, 1 week, and 1 month
MI
-cardiogenic shock (massive infarction), CHF, arrhythmias
Coagulative necrosis
-arrhythmia
1 day
inflammation (neutrophils then macrophages)
- fibrinous pericarditis (chest pain with friction rub)
- rupture of ventricular free wall (tamponade) or interventricular septum (shunt) or papillary muscle (mitral insuff)
1 week
granulation tissue
1 month
scar (type 1 collagen)
-aneurysm, mural thrombosis, Dressler syndrome
What is Dressler’s syndrome
after an acute MI (when a scar forms after about a month) theoretically what happens is during damage antigens are released and you get antibodies made to your own pericardium (pericarditis)
what structural heart abnormality is associated with fetal alcohol syndrome?
VSD
What structural heart abnormality is associated with Down Syndrome?
ASD (ostium primum type)
what structural heart abnormality is associated with congenital rubella?
PDA
asymptomatic at birth but later in life its a holosystolic MACHINE like murmur
in eisenmenger syndrome you can get lower extremity cyanosis because the connection occurs after the major branches of the aorta
Prostaglandin E keeeeeeps the PDA open, thus tx= indomethacin(inhibits PGE)
“boot shaped heart” on CXR suggests what?
Tetrology of fallot
What structural heart abnormality is associated with maternal diabetes?
transposition of the great arteries
treat with prostaglandin E to keeeeep the PDA open
What structural heart abnormality is associated with coarctation of the aorta?
Turner’s syndrome
infantile form, also associated with a PDA
coarctation is between the arch and PDA (lower extremity cyanosis)
what is the adult form of coarctation of the aorta associated with?
bicuspid aortic valve
No PDA
coarctation is distal to the aortic arch (thus HTN in BUE and weak pulses in BLE)… shows up as notching of the ribs on CXR because the collateral vessels form across the intercostals and they get engorged
in ARF, what is the causes the molecular mimicry that causes damage
antibodies to M protein resemble human tissue
What are the JONES criteria?
What you need to diagnose ARF
prior GAS infection (ASO or anti DNase B titer)
minor criteria (fever, elevated ESR)
Major criteria: J (joints- migratory polyarthritis) O (heart problems- draw O like a heart... pancarditis: endocarditis, myocarditis, pancarditis) N (nodules- subcutaneous) E (erythema marginatum) S (sydenham chorea)
Heart=pancarditis leaving vegetations and damaging mitral valve (+/- aortic valve), anschoff bodies in myocardium with anitschkol cells (myocarditis is what kills patients)
friction rub from pericarditis
Chronic rheumatic fever can happen how
relapse of the acute phase over and over by repeat exposures to GAS
you get chronic rheumatic valve disease
mitral stenosis +/- aortic stenosis (fusion of the commissures= “fish mouth appearance”)
complication is endocarditis
describe the murmur of aortic stenosis
systolic ejection click followed by a crescendo-decrescendo murmur
what STD causes aortic regurg due to aneurysm of the aortic root?
tertiary syphilis infection
Aortic regurg= early blowing diastolic murmur… they get “hyperdynamic circulation”= bounding pulses, pulsatile nail beds, and head bobbing (due to widened pulse pressure)
What causes eccentric hypertrophy
LV dilation
basically hypertrophy of one part of the ventricle not the entire concentric ventricle
what valve problem causes a mid systolic click
MVP
the click sound is like a parachute opening due to pressure
usually asymptomatic but if severe then replace the valve
What are “heart failure cells”
hemosiderin laden macrophages
Name a few relationships between bugs and infective endocarditis
strep viridans = IE in previously damaged valves s/p dental procedures
staph aureus = IE of tricuspid valve in IV drug users
staph epidermidis= IE of prosthetic valves
strep bovis= IE in patients with underling colon cancer
IE with negative blood cultures= HACEK organisms (theyre difficult to grow) Hemophilus Actinobacillus Cardiobacterium Eikenella Kingella
What are Janeway lesions and Osler nodes
with IE you can get vegetations that break off and become septic emboli
consequences of septic emboli:
Janeway lesions (non tender red lesions on palms and soles)
Osler nodes (painful lesions on fingers and toes)
splinter hemorrhages of the nail beds
What is Libman Sacks Endocarditis
Sterile vegetations on both sides of the mitral valve associated with SLE
results in mitral regurg
Causes of dilated cardiomyopathy
#1= idiopathic genetic mutation myocarditis (coxsackies virus) alcohol abuse drugs (doxorubicin, cocaine) pregnancy
Causes of Hypertrophic Cardiomyopathy (HOCM)
genetic mutation in sarcomere proteins
AD
histo= myocyte dysarray
Causes of restrictive cardiomyopathy
Amyloidosis sarcoidosis (granulomas) hemochromatosis (iron) endocardial fibroelastosis (children) Loeffler syndrome (eosinophil infiltration of the heart leads to fibrosis of the endocardium and myocardium)
EKG= low voltage EKG with diminished QRS amplitude
What is a myxoma
benign cardiac tumor made of mesenchymal proliferation with a gelatinous appearance
histo= abundant ground substance
most common primary cardiac tumor in adults
in LA as pedunculated mass… blocks mitral valve and causes syncope
What is a rhabdomyoma
benign cardiac tumor (hamartoma) of cardiac muscle
Most common primary cardiac tumor in children, associated with tuberous sclerosis
ventricular tumor
What cancers metastasize to the heart?
breast
lung
skin
lymphoma
goes to pericardium and causes a pericardial effusion
Name all of the vitamin B’s by their name and number
Vitamin B’s are water soluble
1= thiamine
decarboxylation of alpha keto acids (carb metabolism)
(beriberi- periph neuropathy and HF….. wernicke korsakoff syndrome)
2= riboflavin
mitochondrial electron carrier (FMN, FAD)
(angular cheilosis, stomatitis, glossitis… anemia)
3= niacin
electron transfer reactions (NAD/NADP)
(Pellagra-dermatitis, dementia, diarrhea the three “D”s…. peripheral neuropathy)
6=pyridoxine
transamination of amino acids (AA synthesis)
(cheilosis, stomatitis, glossitis)
9= folate/folic acid
hydroxymethyl/formyl carrier (purine and thymine synthesis)
(megaloblastic anemia… neural tube defects)
12= cobalamin
isomerase and methyltransferase cofactor (DNA and methionine synthesis)
(megaloblastic anemia…. neurologic deficits)
what two/three diseases are caused by thiamine deficiency (B1…“to thy 1 B true”)
Beriberi
(infantile vs adult)
(dry vs wet)
infantile= 2-3 m old with cardiac symptoms, cyanosis, SOB, vomiting adult= dry or wet dry= peripheral neuropathy (sensory and motor) wet= peripheral neuropathy + cardiac symptoms (CHF symptoms)
Wernicke korsakoff syndrome (CNS problems in alcoholics) confusion ataxia oculomotor eye movement issues permanent memory deficits
Describe scurvy
vit C (ascorbic acid) def
petechial hemorrhages
gingival swelling
impaired wound healing
weak immune response
rash at the base of hair follicles
what is cheilosis
dry scaling and fissuring of the mouth at the lips and corners
Characteristic of riboflavin def (B2) or pyridoxine def (B6)
B2 also has anemia
Which anti-arrhythmic drugs work on which phases of the cardiac AP?
Class 1 (procainamide, flecainide, lidocaine) work on phase 0- rapid depolarizaiton
Class IV drugs, aka CCBs (verapamil, diltiazem… nondihydropyridines) work on phase 2-plateau phase (L-type calcium channels)… negative inotropes
Class III (amiodarone, sotalol, dofetilide) work on phase 3- late repolarization by potassium… prolong repolarization/AP duration/CT interval and maintain sinus rhythm in paroxysmal afib
What is Osler-Weber-Rendu syndrome?
Its another name for hereditary hemorrhagic telangiectasia (pink spider like lesions
to the skin and mucosal membranes….rupture of which cause bleeding)
AD
affects lips, nose, oral, resp, GI, GU (rarely brain, liver, spleen)
What is Von Recklinghausen’s disease?
same thing as neurofibromatosis type 1
inherited peripheral nervous system tumor syndrome
they get neurofibromas, optic nerve gliomas, lisch nodules (pigmented nodules of the iris), and cafe au lait spots
Describe neurofibromatosis type 2
AD nervous system tumor syndrome
bilateral cranial nerve 8 schwannomas and multiple meningiomas
What is Sturge Weber syndrome
encephalotrigeminal angiomatosis
rare congenital neurocutaneous disorder with cutaneous facial angiomas and leptomeningeal angiomas
mental retardation, seizures, hemiplegia, skull radiopacities with characteristic “tram track” calcifications
Describe Von Hippel Lindau
rare AD condition of tumors and cysts
capillary hemangioblastomas (retina or cerebellum), cysts or cancers in the kidney, liver, and pancreas
at risk for bilateral renal cancer
What is Tuberous sclerosis
AD tumor syndrome with cutaneous angiofibromas (adenoma sebaceum), visceral cysts, and hamartomas
also get renal angiomyolipomas and cardiac rhabdomyomas
complications include seizures
cysts to kidney, liver, and pancreas
CNS hamartoma
What is isolated systolic hypertension? (ISH)
high systolic BP and normal diastolic BP
seen in patients above 60 yo and is responsible for 60-80% of HTN in the elderly
systolic BP >140 is an important modifiable risk factor for stroke and heart disease
ISH is due to increased arterial stiffness,
aka decreased compliance of arteries (including the aorta) associated with aging (also associated with endothelial dysfunction, decreased elastin, and increased collagen deposition)
other causes of ISH are increase in CO due to severe aortic regurg or other causes (anemia, hyperthyroidism)
how would renal artery atherosclerosis/stenosis affect blood pressure?
in would activate RAAS
the increased volume and intreased TPR would elevate both systolic and diastolic BP
How do AV shunts (created by an AV fistula) affect the heart
cardiac pressure volume loops represent the left ventricle
AV shunts increase cardiac preload
(because they bring blood back to the venous system faster)
AV shunts also decrease afterload
(because the blood bypasses arterioles and thus lowers total peripheral resistance)
AV shunts:
increase preload
decrease afterload
(preload= right most vertical line… afterload= top most horizontal line)
high volume AV shunts can eventually cause high output cardiac failure
What is the most common cause of coronary sinus dilation?
elevated right sided heart pressure secondary to pulmonary HTN
most heart venous drainage transverses the coronary sinus to the right atrium… it communicates freely with the RA and thus anything that dilates the RA will dilate the coronary sinus
other causes= anomalous venous drainage into the CS and anomalous pulmonary venous return
(pericardial effusion would cause an extrinsic compression of the CS)
describe the cardiac tissue conduction velocity from fastest to slowest
Fastest conduction velocity:
Purkinje system> Atrial muscle> Ventricular muscle> AV node (slowest)
mnemonic:
Park At Venture AVenue
impulse goes from SA node–> atrial myocardium–>AV node (slowest…delay allows for ventricles to fill during diastole)—> His purkinje system (fastest to ensure that ventricles contract in the bottom up fashion)—> ventricular myocardium
What hemodynamic changes are caused by nitrates?
Nitrates treat the chest pain of chronic stable angina
Nitrates exert their effects by direct smooth muscle relaxation resulting in:
vasodilation (vein>arteries)
*decreased preload (by decreasing LV end diastolic volume)
modestly decreased afterload
mild coronary artery dilation and reduction of vasospasm
*decreased myocardial oxygen demand
Name two cardiac drugs with negative chronotropic effects
beta blockers and non dihydropyridine CCBs
What are four factors in noninflammatory edema in a COPD patient with secondary cor pulmonale
- elevated capillary hydrostatic pressure
- decreased plasma oncotic pressure
- sodium and water retention
- lymphatic obstruction
(moderate increases in interstitial fluid accumulation can be offset by a compensatory increase in lymphatic drainage)… edema really only occurs when the capacity to reabsorp gets overwhelmed
what is the most common cause of aortic stenosis in the US?
a bicuspid aortic valve
harsh crescendo decrescendo systolic ejection murmur best heard in the right second intercostal space with radiation to the carotids
What test is used to evaluate for a cryptogenic stroke?
an echocardiography with a “bubble study” to identify right to left intracardiac shunts
associated with a patent foramen ovale (PFO) or an ASD
PFO= incomplete fusion of the atrial septum primum and secundum
(normal fusion is induced with umbilical cord clamping and decreased pulmonary vascular resistance which lowers RA pressure and increases LA pressure)
incomplete fusion in 25% of normal adults
right to left shunt (with a clot) can occur with valsalva release which raise RA pressure above LA pressure
PFOs are much more common than ASD
What does reperfusion injury look like after DVT clot removal from a calf?
thrombus extraction followed by a rapid surge of serum creatine kinase (due to cell membrane damage)
the cells within the damaged tissue paradoxically die at an accelerated pace through apoptosis or necrosis after resumption of blood flow
mechanisms of reperfusion injury:
- oxygen free radical generation
- severe irreversible mitoch damage (“mitoch permeability transition”)
- inflammation attracting neutrophils that cause damage
- complement pathway activation
* creatine kinase gets into circulation when the cells are injured
True or false:
Glutathione peroxidase worsens cellular injury through free radicals
false
glutathione peroxidase reduces cellular injury by catalyzing free radical breakdown
acetaminophen overdose liver toxicity is when glutathione peroxidase gets overwhelmed
what bug makes dextrans, causes IE, and is GPC?
strep viridans
associated with dental caries
DEntal… DExtrans
what bug causes ARF, glomerulonephritis, and migratory polyarthritis
GAS pyogens
What is isoproterenol?
a nonselective beta agonist
increases cardiac contractility (positive inotrope)= beta 1
decreases vascular resistance and arterial blood pressure (due to vasodilation)
Describe the effects of acetylcholine
binds M2 in the heart (lowers HR, slows conduction velocity) M3 in the vasculature (vasodilation indirectly via NO)
Describe the effects of adenosine
activates potassium channels increasing potassium conductance (leads to transient conduction delay through the AV node)
also causes peripheral vasodilation and decreases contractility
Describe the effects of clonidine
alpha 2 agonist in the brainstem
leads to decreased SNS outflow
leads to decreased peripheral resistance, decreased HR, and decreased BP
Describe the effects of esmolol
beta 1 blocker
negative inotrope
negative chronotrope
describe the effects or norepi
alpha 1 agonist with mild beta 1 agonist properties
thus vasoconstriction and increased contractility
Describe the effects of phenylephrine
sympathomimetic drug with pure alpha agonist activity
vasoconstriction
What are the major ADRs with dihydropyridine CCBs?
(amlodipine, nifedipine)
effective anti HTN monotherapy
ADRs= peripheral edema
flushing
dizziness
headache
peripheral edema= preferential dilation of arterioles (increases hydrostatic pressure and fluid extravasation)
ACEI and ARBs block RAAS which leads to venodilation and can normalize the increased hydrostatic pressure caused by the CCB
Describe the effects of alpha1 and alpha2 stimulation
alpha 1=
vasc sm m contraction, mydriasis (pupil dilation), increased internal urethral sphincter tone and prostate contraction
increase in BP with reflexive (delayed) decreased HR (baroreceptor stimulation increasing PNS on heart and PNS inhibits SA node activity to slow conduction through AV node to decrease contractility)= alpha 1 agonist (phenylephrine, methoxamine)
alpha2=
CNS mediated decrease in BP, decreased IOP, decreased lipolysis, decreased norepi release, increased platelet aggregation
complications of a bicuspid aortic valve
the abnormal shape causes increased hemodynamic stress which accelerates normal aging and causes premature atherosclerosis and calcification of the aortic valve
The deposits accumulate as early as adolescence and lead to aortic stenosis in >50% patients (symptoms on average begin around 50 yo….10 years premature)
What is subclavian steal syndrome?
significant stenosis of the subclavian artery before branching into the vertebral artery…
subclavian stenosis is due to atherosclerosis #1 (also takayasu arteritis and complications of heart surgery)
the low pressure on the other side of the stenosis causing blood to flow from the vertebral to the subclavian (and “stealing” blood from the other vertebral artery (and thus away from the brainstem)
symptoms: asymptomatic arm ischemia vertebrobasilar insufficiency (dizz, vertigo, drop attacks) signif BP difference between arms
What is coronary subclavian steal phenomenon?
Similar to subclavian steal syndrome except that its in patients with hx of CABG using the internal mammary artery
blood flow through the IMA can reverse and steal from the coronary circulation during increased demand
Symptoms would reflect coronary ischemia
