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
Where is the AV node located in the heart?
in the inter-atrial septum near the opening of the coronary sinus
on the endocardial surface of the RA near the insertion of the septal leaflet of the tricuspid valve and the orifice of the coronary sinus
(sort of the wall between the atria, near the bottom and somewhat posterior)
where is the SA node located?
upper anterior right atrium at the opening of the superior vena cava
what are the mediators of vasodilation at the level of the vascular endothelium
mediators: acetylcholine bradykinin serotonin substance P shear stress forces
these activate receptors on endothelial cells that increase cytosolic calcium which activates the conversion:
arginine + NADPH +O2—–(eNOS)—->NO + citrulline
NO diffuses into adjacent smooth muscle cells and increases guanylyl cyclase> increase cGMP> protein kinase G> reduction in cytosolic calcium> relaxation of vascular smooth muscle
what is the difference between HTN urgency and emergency?
emergency also shows signs of end organ damage
ACS encephalopathy pulmonary edema AKI brain hemorrhage aortic dissection eye problems
Describe the drug fenoldopam
short acting, selective, peripheral dopamine 1 agonist
(no effect to alpha or beta receptors)
DA1 stimulation increases adenylyl cyclase which increases cAMP —-> vasodilation of most arteries (leading to decrease in systemic BP)
vasodilation is prominent in the kidney for fenoldopam which increases renal perfusion and natriuresis (helpful for HTN emergency with AKI)
Why is hydralazine not used in HTN emergency?
hydralazine is a direct arteriolar vasodilator with no effect on kidney perfusion/natriuresis
not used in HTN emergency because it is associated with reflex SNS activation (which increases HR and contractility and causes sodium/water retention)
What precautions are taken to reduce infection of central venous catheters?
main infections come from patient’s skin or health care worker’s hands (gram positive cocci infect most… staph aureus and coag neg staph)
CDC recommends:
1. hand hygiene with alcohol sanitizer or soap prior to sterile gloves
2. barrier precautions (including surgical drape)
3, prepare insertion site with chlorhexidine antiseptic
4. use subclavian or internal jugular (femoral vein infected more often)
5. promp removal when not needed
upon ischemia, how long does it take the affected portion of the heart to stop contracting?
about 60 seconds of total myocardial ischemia
(aerobic glycolysis becomes anaerobic within seconds, not enough ATP is made and depletion is rapid, and lactate builds up)
when ischemia lasts less than 30 minutes, loss of contractility (“myocardial stunning”) is reversible (returning to normal over hours to days)
during the hypoxia, ATP –>–>–>adenosine which vasodilates to meed myocardial demand (but adenosine gets depleted, cellular homeostasis fails, and ischemic injury becomes permanent)
What does the murmur of a PDA sound like?
continuous murmur heard best in the left infraclavicular region with maximal intensity at S2
PDA most often seen in premature babies and cyanotic congenital heart disease
After stabilization, what is the long term treatment for HFrEF
Beta blockers
(carvedilol, metoprolol)
because it improves survival in patients with HF due to LV systolic dysfunction, it also decreases myocardial oxygen demand by reducing contractility and slowing ventricular rate… it also decreases afterload
improves survival due to limiting cardiac remodeling
only use Beta Blockers after the patient is stabilized otherwise it could impair CO
other drugs that improve long term survival in HF patients:
ACEI
ARBs
Aldosterone antagonists (spironolactone, eplerenone)
What is the mechanism of VRE? (vancomycin resistant enterococcus)
Vancomycin normally works by binding “D-ala-D-ala” terminals in the bacterial cell wall and preventing the formation of peptidoglycan (inhibits the second stage of cell wall synthesis)
resistance to vanco occurs when the cell wall precursor proteins change their cell wall structure from “D-ala-D-ala” into “D-ala-D-lactate” so it screws up the vancomycin’s binding site
What are the two mechanisms that bugs become resistant to penicillin
- beta lactamases (penicillinase) are made by the bug and used to destroy the penicillin’s beta lactam ring making the drug ineffective
(cephalosporins, carbapenems, and penicillinase resistant penicillins like nafcillin and methicillin are not susceptible to the actions of penicillinase) - some bugs have modified penicillin binding proteins in their peptidoglycan cell walls which don’t allow beta lactam antibiotics to bind and work
(this is MRSA’s resistance mechanism)
What kind of antibiotic is cycloserine?
bacterial cell wall synthesis inhibitor
rarely ever used because its super ototoxic
cycloserine inhibits the incorportation of D-ala into the UDP-MUrNAc-oligopeptide during cell wall synthesis
how does the antibiotic polymyxin work?
polymyxin binds to the cytoplasmic membrane and disrupts it/interfering with the permeability of the membrane
how does the antibiotic tetracycline work?
inhibits protein synthesis by binding the 30S subunit and inhibiting binding of aminoacyl-tRNAs
how do bugs become resistant to tetracycline?
increased efflux of the drug from within the bacterial cell via active-efflux pump or by production of a protein that allows translation to take place even when tetracycline is present within the bacterium
how does the antibiotic amikacin work?
amikacin is an aminoglycoside
aminoglycosides inhibit the 30S subunit preventing bacterial protein synthesis
how do bugs become resistant to aminoglycosides?
by inactivation through aminoglycoside modifying enzymes
these enzymes are largely plasmid encoded and serve to phosphorylate, adenylate, or acetylate the abx and thus lead to decreased ability of the abx to bind the ribosomal subunits
pseudomonas are resistant to aminoglycosides by decreasing their entry into the bacterium
how is sildenafil (aka viagra) similar to BNP?
They have similar intracellular signaling
Atrial and Brain natriuretic peptides (ANP and BNP) bind ANP receptors which are linked to guanylyl cyclase—> increase CGMP—> vasodilation
NO activates the same cGMP as the guanylyl cyclase from ANP and BNP
Penile erection is initiated by Ach and NO from PNS leading to increase cGMP and vasodilation of arteries supplying the corpus cavernosum
sildenafil is a phosphodiesterase 5 inhibitor that stops degredation of cGMP thus enhancing the effect of PNS activation on erectile tissues
what happens when you coadminister sildenafil and nitrates?
because nitrates (nitroglycerin, isosorbide mononitrate) work by releasing NO and sildenafil prevents cGMP degredation (which is the next step beyond NO release) you can get excessive cGMP induced vasodilation and severe hypotension
what mutation causes congenital long QT syndrome?
LQT type 1 and LQT type 2
(due to genetic mutations in k+ channel proteins that contribute to the outward rectifying potassium current)
decreased outward potassium causes prolonged refractory period, prolonged AP duration, and prolonged QT
complications= torsades (ventricular arrhythmia) palpitations syncope seizures sudden cardiac death
orthopnea is a specific sign for what?
left sided heart failure
What is a complete atrioventricular (AV) canal defect and what is it associated with?
failure of endocardial cushion fusion results in an ostium primum ASD, a VSD, and a single AV valve
(this leads to left to right shunt, AV valve regurg, excess pulmonary blood flow, and HF symptoms)… AV valve regurg= holosystolic murmur best heard at the apex… increased pulm blood flow= mid diastolic rumble
most common cardiac defect in down syndrome (autosomal trisomy)
what is 22 q 11 deletion syndrome and what heart abnormalities is it associated with?
DiGeorge syndrome (thymic aplasia, T cell def, hypoparathyroidism, hypocalcemia)
associated with TOF, truncus arteriosus, and transposition of the great arteries
what heart abnormality is associated with marfan syndrome
marfan= fibrillin 1 mut
associated with cystic medial necrosis of the aorta (resulting in aortic dissection and aortic valve regurg)
also can cause MVP
what heart abnormality is associated with friedreich ataxia
friedreich ataxia= mut in frataxin, a mitochondrial protein important for iron homeostasis and resp function
characterized by spinocerebellar degeneration
associated with HOCM
what heart abnormality is associated with tuberous sclerosis
tuberous sclerosis= mut in tuberin and hamartin
develop cardiac rhambdomyomas in the heart
they also get cutaneous angiofibromas, CNS hamartomas, and renal cysts
what two heart abnormalities are associated with Turner syndrome
bicuspid aortic valve and coarctation of the aorta
What effect do non dihydropyridine CCBs (aka antiarrhythmics class IV) do to cardiac pacemaker cells?
class IV anti arrhythmics (NDHP CCBs) block L type calcium channels in cardiac slow response tissues which cause slowing of phase 4 spontaneous depolarization
phase 4 slanted slower upstroke is controlled by sodium (funny current) and calcium (T type and L type)
describe the change in afterload, preload, and LV EF in a heart with severe acute mitral regurg compared to a normal heart
afterload decreased
preload increased
LV EF increased (frank starling says that an increased preload and a decreased afterload result in an increased ejection fraction)… but much of the stroke volume is lost to regurg meaning a reduced cardiac output and thus cardiogenic shock
Frank Starling:
contractility is directly proportional to end diastolic volume (preload)… increase preload and or decrease afterload= increase contractility (which increases ejection fraction)
what is the difference between type A and type B aortic dissections
A= involves ascending aorta
B= only the descending aorta
brachial BP discrepancy suggests compromise of the brachiocephalic trunck on the arm with the lower BP
risk factors= HTN (medial hypertrophy of aortic vasa vasorum and reduced blood flow to the media… leads to degeneration, dilation and stiffness, increased wall stress, and ultimately an intimal tear and dissection
What is monkeberg sclerosis?
medial calcific sclerosis
a form of arteriosclerosis characterized by calcium deposits in the medial layer of muscular arteries…. may cause ISH due to arterial hardening
clinically asymptomatic and insignificant (think mammograms)
what does tertiary syphilis do to the aorta
causes a form of aortitis characterized by obliterative endarteritis of the vasa vasorum
(this as well as aortitis with medial inflammation from autoimmune conditions like takayasu and giant cell arteritis) cause weakening of the aortic wall and predispose aortic aneurysm»dissection
why is aspirin the treatment for stable angina (angina pectoris) and what is the next best option if aspirin is not tolerated?
aspirin decreases the risk of adverse CV events
irreversible COX1 inhibition prevents synthesis of TXA2 (a potent stimulator of platelet aggregation and vasoconstriction)
ADRs= aspirin can exac pre existing resp symptoms or cause allergic reactions
next best drug is clopidogrel (an irreversible P2Y 12 blocker) which blocks part of the ADP receptor on the platelet surface so that the platelet cannot aggregate
clopidogrel is as effective as aspirin for prevention of CV events
Describe apixaban and warfarin
apixaban is a direct factor Xa inhibitor that prevents platelet activation and fibrin clot formation
warfarin inhibits an enzyme needed to synthesize active vitamin K which will reduce synthesis of vit K dependent clotting factors (2,7,9,10)
both apixaban and warfarin are used to prevent or treat thromboembolic events (not CAD)
describe cilostazol
a phosphodiesterase inhibitor that is occasionally used in patient’s with symptomatic PVD (ex= claudication)
describe low molecular weight heparins (LMWH; enoxaparin, dalteparin)
indirect thrombin inhibitors that bind with antithrombin and convert it from a slow to rapid inactivator of thrombin and factor Xa
used for patients with ACS (unstable angina or MI)… not for stable angina
describe eptifibatide
its a platelet glycoprotein 2b3a inhibitor that inhibits the final common pathway of platelet aggregation
occasionally used in ACS patients but not stable heart disease
describe naproxen
NSAID used for pain management with osteoarthritis
use of nonselective and selective COX2 NSAIDS increases the risk for adverse CV events
what are the treatments for primary hypertriglyceridemia? (aka high VLDL)
fibrates and nicotinic acid therapy
how does the body try to fix acute decompensated heart failure?
the reduced cardiac output is detected as an initial drop in BP which triggers a compensatory neurohumoral stimulation directed at maintaining BP and tissue perfusion
compensatory response: increased SNS stimulation of RAAS release of antidiuretic hormone (improve CO and contractility, increase fluid, and vasoconstrict)
the increased afterload= exac HF, fluid retention, poor renal perfusion
RAAS= edema, pulm congestion (CHF)
deleterious cardiac remodeling
Describe BNP and its actions
Brain natriuretic peptide
released by ventricles in response to stretching (volume overload)
helps to diagnose CHF exacerbation
(like ANP) it causes: vasodilation natriuresis decrease in BP (to alleviate the symptoms of HF)
is S4 pathologic in young patients
yes always
(unlike S3)
auditory question of an S4 heart sound in a 65 yo man with long history of HTN, DM2, and ex-smoker (otherwise he exervises and has normal BMI)… heart sound heard at the apex
s4= left ventricular hypertrophy or restrictive cardiomyopathy
What do you see on histo as a result of hypertensve crisis/emergency
onion like concetric thickening of arteriolar walls
= “hyperplastic arteriolosclerosis”
due to laminated smooth muscle cells and reduplicated basement membranes
this can lead to renal arteriolar stenosis and activation of RAAS worsening the vicious cycle
patients can also have hypertensive encephalopathy (HA, irritable, ALOC, CNS dysfunction)
which has more oxygen content:
coronary sinus venous blood or pulmonary artery blood
more oxygen in pulmonary artery
because the heart is so great at extracting oxygen from the blood (better than any other organ in the body), the cardiac’s veins have the least oxygen of any blood in the body (more than systemic venous blood)
because pulmonary artery has a mixture of coronary sinus venous blood and systemic venous blood it thus has more oxygen
What drug is used for afib which prolongs QT interval yet has a super low incidence of torsades than any other QT prolonging agent?
amiodarone (class 3 anti arrhythmic)… the one with properties off all the four classes
the low incidence of torsades is due to a more homogeneous effect on vantricular repolarization compared to the other drugs
which part of the EKG tracing is affected during normal sinus rhythm when they have an abnormal conduction pathway in the heart that bypasses the AV node
AT BASELINE:
the PR interval (not just the P wave alone)… pre excitation=short PR interval with an early upslope of the QRS “delta wave”, and a wide QRS
this 21 year old male probably has WPW syndrome (pre excitation syndrome and the most common re entry circuit responsible for recurrent paroxysmal narrow QRS atrial tachycardia… when being affected QRS narrows)
the accessory conduction pathway= bundle of kent
Describe enterococcal endocarditis
elderly men who recently underwent cystoscopy (GU)
or colonoscopy or obstetric procedure
Enterococci cause UTI (#1), intra abdominal and pelvic infections, and wound infections
gamma hemolytic (aka no hemolysis on agar)
catalase negative (formerly a strep species)
pyrrolidonyl arylamidase positive
Lancefield group D gram positive cocci
grow in HYPERTONIC 6.5% SALINE AND BILE
enterococcus faecalis (80-90%) and enterococcus faecium (10-15%)
super hard to treat because resistant to lots of abx
tx= ampicillin (cell wall active agent) and an aminoglycoside
what is the left atrial appendage?
small saclike structure in the LA that is particularly susceptible to thrombus formation
define permissiveness
when one hormone allows another to exert its maximal effect
ex= norepi alone produces a limited degree of vasocontriction but when pretreated with cortisol (which has no vasoactive effect alone), norepi vasocontriction was markedly increased
here, cortisol was upregulating alpha 1 receptors on vasc smooth muscle cells (it makes sense then that low cortisol levels seen in adrenal insuff will contribute to hypotensive crisis by decreasing vasc responsiveness to angiotensin 2 and norepi)
define synergistic or additive effect
combining two drugs with similar action
additive= sum of two individual drugs effects
synergistic= when the combined effects exceeds the sum of the individual drugs
how does cortisol exert permissive effects for other hormones
helps improve response to a variety of stressors
cortisol increases vasc and bronchial smooth muscle reactivity to catecholamines
cortisol increases glucose release by the liver in response to glucagon
define tachyphylaxis
the decreased drug responsiveness in a short period following one or more doses
(aka rapidly developing tolerance)
a young asymptomatic patient with a soft systolic ejection murmur at the right second intercostal space most likely has what valve issue
bicuspid aortic valve
the aortic valve opens and the LV pressure continues to rise in the beginning of systole with forward blood into the aorta
What are the class 3 anti arrhythmics
sotalol (beta blocking properties too)
amiodarone
dofetilide
symptoms of giant cell (temporal) arteritis
jaw claudication
headache
facial pain
vision loss
biopsy= granulomatous inflammation of the media (also seen in takayasu arteritis which affects the aortic arch and sometimes its branches, this is in young females less than 40 yo)
patients 50 yo+
give examples of leukocytoclastic vasculitis
characterized by segmental fibrinoud necrosis of the small vessels
microscopic polyangiitis
microscopic polyarteritis
hypersensitivity vasculitis
describe polyarteritis nodosa (PAN)
segmental transmural necrotizing inflammation of medium to small sized arteries
necrotic tissue and deposits of immune complexes, complement, and plasma proteins cause a fibrinoid necrosis (consistent with immune complex vasculitis)
what is buerger’s disease (thromboangiitis obliterans)
thrombosing vasculitis of medium and small sized arteries (principally the tibial and radial arteries)
commonly seen in heavy cigarette smokers with onset before age 35
the smoking disease in young people that causes auto amputation of fingers and toes
what is buerger’s disease (thromboangiitis obliterans)
thrombosing vasculitis of medium and small sized arteries (principally the tibial and radial arteries)
commonly seen in heavy cigarette smokers with onset before age 35
the smoking disease in young people that causes auto amputation of fingers and toes
myxomatous degeneration with pooling of proteoglycans in the media layer of arteries is associated with what disorder
Marfan syndrome which is associated with aortic aneurysms and dissections
myxomatous changes= pathologic weakening of connective tissue (found in cystic medial degeneration= basket weave pattern of elastic tissue)
marfan syndrome is a frequent cause of cystic medial degeneration in young patients.
its AD defect in extracellular glycoprotein fibrillin1 (which helps form scaffolding for elastic fibers)
beta aminopropionitrile (a chemical found in sweet peas) causes inhibition of lysyl oxidase (which cross links elastin and collagens) and can cause changes in the elasticity of the aorta that mimics the myxomatous degeneration seen in marfans syndrome
what is jervell and lange nielsen syndrome
AR congenital long QT syndrome with cong sensorineural deafness too
what are the main regulators of mean arterial pressure when it is low?
increased SNS and RAAS (low BP detected by the baroreceptor firing (picked up by the medullary vasomotor center) and by the JGA detecting low renal perfusion)
what infectious disease can cause a third degree heart block?
lyme disease
what does ANP do?
released from a stretched atria telling kidneys to pee out volume and relax vasculature cause its overwhelmed
what do you expect to happen to someone’s morning plasma renin activity measurement after being prescribed an ACEI or ARB compared to a diuretic?
ACEI/ARB= blocking the RAAS pathway would cause a feedback increase in serum renin levels
Diuretic= induced hypovolemia decreases renal blood flow which increases renin and activates RAAS
low sodium intake woud also increase renin
SNS blockers (beta blockers and clonidine)= reduce renin levels
primary hyper-aldo= would suppress renin production and cause low serum renin levels
plasma renin activity measures the amount of angiotensin 1 generated per time (assesses RAAS)
What is the relationship of the IVC to the right renal artery?
an axial CT of the abdomen near L1 shows that the IVC lies anterior (in front of) the right renal artery (and also anterior to the aorta)
the IVC is formed by the union of the right and left common iliac veins at L4-L5 and drains into the right atrium at the level above the diaphrage T8
What murmur do you listen for if you suspect a paradoxical embolism causing stroke?
venous clot heads to the brain when there is a PFO, ASD, VSD, or large pulmonary arteriovenous malformation
murmur= left to right shunting causing a wide and fixed S2 splitting
ASD can also sound like a [mid systolic ejection] murmur over the left upper sternal border due to increased flow across the[pulmonic valve] and a mid diastolic [rumble] due to increased flow across the [tricuspid valve]
you can have transient reversal of the left to right shunt during high right sided pressure
(aka early systole, straining, coughing, or pooping)
what causes an early diastolic decrescendo murmur improved with amyl nitrite inhalation?
aortic regurg
amyl nitrit causes vasodilation (reduces systemic BP thus reduces regurg flow)
What causes a presystolic murmur that disappears with atrial fibrillation?
mitral or tricuspid stenosis= diastolic murmur with presystolic (aka late diastolic) accentuation due to atrial contraction
in mild stenosis the murmur may only be heard during the accentuation phase in late diastole
afib can cause the murmur to disappear completely
Does inspiration cause a MVP mid systolic click to occur earlier or later?
earlier because there is reduced LV volume with inspiration because there is less blood returning to the left heart
(during inspiration blood rushes to the lungs to be oxygenated and thus away from the heart)
a drug that decreases HR without affecting contractility or relaxation works on what cardiac channels?
funny sodium channels during phase 4 (pacemaker cells)
heart rate drugs: beta blockers non dihydropyridine CCBs digoxin ivabradine
ivabradine is the only one that slows heart rate (negative chronotrope) without inotropic or lusitropic (relaxing) effect
ivabradine= inhibits funny sodium channels to slow SA node firing thus prolonging the slow depolarization phase (4)…
used in certain HFrEF patients with persistent symptoms despite appropriate medications
it reduces risk of hospitalization due to HF
class 1 antiarrhythmics slow conduction velocity but dont signif alter HR class 3 antiarrhythmics dont have a role for management of CHF
a stab wound to the lateral anterior chest wall at the fifth intervostal space along the left midclavicular line would injure what?
the left lung
although the right ventricle is the most anterior, the stab wound being on the vertical nipple line would injure the cardiac apex most likely which is made of the left ventricle
the heart is behind the sternum and is anteriorly covered by the lungs
PMI (point of maximal impulse)= fifth left intercostal space between the fifth and sixth ribs at the left midclavicular line (aka the stab wound aka the apex of the heart)
symptoms of a fully obstructive coronary artery (aka transmural MI)
severe chest pain not relieved with rest or nitroglycerin diaphoresis dyspnea nausea light headedness palpitations
peaked T waves (hyperkalemia)
then ST elevation (minutes to hours)
Q waves hours to days
describe where the lateral, inferior, anterior/septal leads are on an EKG
from top to bottom if the ekg was to draw a line down the middle it goes:
lateral
inferior
anterior/septal
lateral
lateral= I, aVL, V5, V6
inferior= II, III, aVF
anterior/septal= (V3/V4)/ ((V1/V2)
stable angina requires what percentage of the lumen to be obstructed?
75% at least
describe the LV pressure, volume, and EF in diastolic heart failure
LV end diastolic pressure is increased
LV end diastolic volume is normal
LV EF is normal
=problem filling with blood!
diastolic HF is a common cause of acute decompensated HF (when it causes pulmonary issues)
causes= decreased LV compliance (ischemia) or increased wall stiffness (amyloid deposition, hypertrophy)
increased LV end diastolic pressure brings the bottom-most line of the pressure volume loop upwards (to shrink the cycle)
the bottom most line represents compliance
Why can’t I lie on my back
cuts off the IVC
“supine hypotension syndrome” or “aortocaval compression syndrome”
causes hypotension pallor sweating nausea dizziness
occurs >20 weeks gestation
severe= LOC and fetal demise
what medication inhibits metalloprotease neprilysin, promotes natriuresis, and decreases BP by vasodilation?
natriuretic peptides
BNP also protects against the deleterious myocardial remodeling and fibrosis that occurs in HF
Neprilysin is a metalloprotease that cleaves and inactivates endogenous peptides including BNP, glucagon, oxytocin, bradykinin (thus inihibiting neprilysin increases endogenous natriuretic peptides and helps in HF)
what are the normal pressures for each chamber of the heart and the vessels?
SVC and RA= 1-6 mmHg
RV= 15-30 systole/ 1-6 diastole (same as RA)
Pulm artery= 15-30 systole/ 6-12 diastole
PCWP aka LA (“PA occlusion pressure”)= 6-12
LV= 90-140 systole/6-12 diastole
are loud murmurs from big or small VSDs
loud come from small VSDs (asymptomatic patients)
soft or absent come from large VSDs (HF in infancy= difficulty feeding, tachypnea, failure to thrive)
VSD= harsh holosystolic murmur heard at the left lower sternal border
listen to more murmurs online
what does the handgrip maneuver do to a murmur
increases afterload
in the VSD it increases the murmur
describe the effects of inspiration, valsalva strain, abrupt standing, squatting, passive leg raise, and handgrip on the heart
inspiration= increases blood to right heart and decreases blood to left heart
valsalva strain and abrupt standing= decrease preload and afterload
(valsalva= trying to force yourself to exhale really hard while your nose and mouth are shut… to increase intrathroacic pressure)
squatting= increase preload and afterload
passive leg raise= increase preload
handgrip= increase afterload
early diastolic murmur
aortic regurg
systolic crescendo decrescendo murmur
aortic stenosis
wide fixed S2 splitting and systolic ejection murmur
ASD
what does the PDA form when its closed
the ligamentum arteriosum
which blood tests measure which blood coag pathways
aPTT measures intrinsic (12>11>9) + kininogen/kallikrein
PT measures extrinsic
(7) + tissue factor
final common pathway measured by both (10>prothrombin>thrombin>fibrinogen>fibrin>clot)
hemarthroses= bleeding into joint spaces (hemophelia)
hemarthroses and excessive bleeding after a tooth extraction are suggestive of a clotting factor def (coagulopathy)… present with deep tissue bleeding into joints, muscles, and sub Q
platelet def on the other hand cause mucocutaneous bleeding (nose bleed or petechiae)
X linked hemophilia A is what factor def
factor 8 def
isolated prolonged aPTT
what is hemophilia C
factor 11 def
rare AR
isolated prolonged aPTT
hageman factor def is what factor
factor 12
AR disorder
no clinically signif bleeding despite aPTT prolongation
von Willebrand factor causes what blood test abnormalitis
vWF is both a carrier for F8(protection from degredation) and mediates platelet adhesion to the endothelium
prolonged bleeding time
prolonged or normal aPTT
bleeding time indicates platelet function
Describe calcium’s role in the cytoplasm in the heart
L type calcium channels bring calcium into myocytes during depolarization
ryanodine receptors in the sarcoplasmic reticulum sense this and spit out a shit ton more calcium intracellularly
that shit ton extra calcium from the SR diffuses through myofilaments to bind troponin C
this causes tropomyosin to move so actin and bang myosin and contract the muscle
the last stage of excitation contraction coupling is myocyte relaxation where calcium leaves the cytoplasm via the sodium calcium exchange (NCX) and calcium ATPase pump called (SERCA)
NCX removes 1 ca from inside the cell for every 3 sodium going inside the cell
SERCA Ca ATPase actively transfers calcium into the SR by sacrificing ATP
how does calmodulin control calcium
its a calcium binding messenger protein that regulates intracellular calcium activity and transcription factor signalling in smooth muscle cells
(aka not heart or skeletal muscle)
what is the physiology behind cellular swelling in transient myocardial ischemia
myocardial cells increase in size because of intracellular calcium accumulation
during ischemia, ATP causes ion pump failure which causes accumulation of sodium and calcium within the cell (net solute GAIN)
this draws in free water and causes cellular and mitochondrial swelling
which antiarrhythmic preferentially binds rapidly depolarizing and ischemic ventricular myocardial fibers with minimal effect on normal ventricular myocardium
class 1B! (lidocaine)
weakest sodium channel blockers and dissociate the fastest of the class 1 (thus the negligible effects on normal tissues)
they bind sodium channels in the inactivated state
class 1B is great for ischemic induced ventricular arrhythmias because ischemic tissue has a higher resting membrane potential causing delayed recovery from the inactivated state and thus class 1B has increased binding!
What is ibutilide
-tilide drugs are class 3 anti arrhythmics
potassium channel blockers
acute termination of a flutter/fin
prolongs the QT and predisposes torsades
afib has what sudden effect on the LV
sudden decrease in LV preload
(causing severe hypotension and acute pulmonary edema)
thus cardioversion is indicated for acute afib in severe aortic stenosis patients (sudden HF precipitated by acute afib in 10% of AS patients)
describe the letters on the jugular venous tracing then look at a picture
remember this looks at the right heart
a= Atrial contraction (notably absent in afib patients)
c= ventriCular Contraction and bulging of the triCuspid
x= atrial relaXation
v= Venous blood passively filling the right atrium
y= passive emptYing of the RA into the RV before contraction
describe constrictive pericarditis on CT
thickening and calcification of the pericardium (white around the enlarged heart)
causes a rapid Y descent (deeper and steeper passive RA emptYing)
causes= radiation, cardiac surgery, tuberculosis
What is ortner syndrome
mitral stenosis (mid diastolic rumble) causes LA dilation sufficient to impinge on the left recurrent laryngeal nerve (hoarseness)
neurapraxia=failure of nerve conduction due to injury (by the LA in this case)
What kind of drug widens the QRS complex during exercise when it should normally be reduced (accompanying faster HRs)
drugs that exhibit strong use dependence (lengthens the QRS duration in a rate dependent manner)
ex= flecainide (flakes)
class 1C anti arrhythmics (treats atrial tachycardias)... bind fast sodium channels to prolong QRS
class 1c are the slowest to dissociate and thus have the strongest use dependence (sodium blocking effects intensify as the HR increases due to less time for medication to dissociate from the receptor).... at high HR they can prolong the QRS (which can be proarrhythmic)
class 3 agents show reverse use dependence (slower the HR the more the QT interval is prolonged)
CT showing compression of the left renal vein between the superior mesenteric artery and the aorta predisposes what vascular abnormality?
varicocele
compression causes retrograde blood flow to the testes and dilation of the pampiniform plexus… compression could also be due to a mass
“nutcracker effect”
also causes hematuria, flank pain, or abdominal pain (kidney stone presentation ish)
holosystolic murmur at the apex radiating to the axilla is what (also known as a diastolic rumbling)? and what is the best indicator of severity?
mitral regurg
indicator=
doppler echocardiograph
but easier than that is to look for an S3
(would indicate severe mitral regurg when there is an S3 because that means there is LV volume overload)
mid systolic click
MVP
How do beta blockers lower BP
- reduce myocardial contractility and HR
- decrease renin release by the kidney***
useful for HTN patients with comorbidities like: migraine essential tremor stable angina prior MI afib
SNS increases renin via beta 1 receptors on JGA cells, thus beta blockers like metoprolol inhibit renin release
which antiarrhythmic causes QRS prolongation with little effect on QT duration
class 1C is one of the only one that widens QRS complexes (because they block sodium channels)… class 1 A a little bit of QRS widening but has significant QT prolongation
QRS= ventricle depolarization (aka phase 0 in the cardiac myocyte AP)
QT interval= ventricular depolarization and repolarization (total duration of the ventricular AP)… but since depolarization is so rapid, QT interval basically just measure ventricular repolarization
1C= flecainide (flakes) and proafenone (purple phone)…
what drugs block phase 3 of the cardiac myocyte
class 3 antiarrhythmics (amiodarone, sotalol, dofetilide)
causes QT prolongation
what does increasing cAMP do?
the activated Gs subunit activates adenylyl cylase which turns ATP into cAMP…
increased cAMP activates protein kinase A…
basically cAMP= contraction or signalling
so a beta 1 blocker atenolol will decrease cAMP in the heart (less contractility and signalling), will decrease cAMP in JGA cells (less signalling because renin is blocked and less contraction theoretically if renin is being squeezed out) and will have no effect on vasc smooth muscle cAMP (because there are no beta 1 receptors in the vasc)
beta 2 receptors found in vasc and bronchial smooth muscle
(propranolol is a beta 1 and 2 blocker)
What are the two GPCR signalling pathways
cAMP (Gs»»increased cAMP»> PKA»»contraction/signalling)
phosphatidylinositol (Gq»>PLC»>degrates membrane lipids into DAG and IP3»>calcium release from SR)
patient with albuminuria started on an ACEI to prevent worsening diabetic nephropathy develops orthostatic hypotension the next day, why?
ACEI can cause first dose hypotension (significant in patients with volume depletion or heart failure… such as those taking diuretics because they have high renin and the ACEI causes abrupt removal of ang2 vasocontriction which results in drop in peripheral vasc tone and precipitous drop in BP)
to prevent this, therapy should be started at a low dose and titrated up
kidneys arent the answer because creatinine levels are fine
what are you at risk for if you have persistent lymphedema?
lymphangiosarcoma
rare malignant neoplasm of the endothelial lining of lymphatic channels
due to chronic dilation of lymphatic channels
what is a cystic hygroma and what is it associated with
macrocytic lymphatic malformation associated with turner syndrome
occur in children at the neck or axilla
what is a nevus flammeus
a port wine stain
birthmark with malformed dilated blood vessels in the superficial dermis
permanent
what is kaposi’s sarcoma and what is is associated with
hyperplasia or neoplasm of spindle shaped cells (containing markers of smooth muscle and vascular endothelial damage)
associated with HIV and immunocompromised states
what is a liver hemaniosarcoma assocated with
its a rare malignant vascular endothelial cell cancer
associated with carcinogens like:
arsenic (pesticides)
thorotrast (former radioactive contrast medium)
polyvinyl chloride (plastic widely used in industry)
What is a juvenile hemangioma
also called a strawberry type hemangioma
cutaneous, small, bright red, slightly elevated lesion (here on a baby butt)…
benign vasc tumor that over time will first increase in size (in proportion to the child) then regress spontaneously at or before puberty (typically fade 1-3 yo)… 95% gone by 7 yo
composed of unencapsulated aggregates of closely packed thin walled capillaries
What causes the obstruction in HOCM
the interventricular septum and the MITRAL VALVE LEAFLET
harsh cresc-decresc systolic murmur at the apex and left sternal border that changes with intensity with maneuvers
What is Kussmaul sign (NOT breathing)
in a patient with constrictive pericarditis (due to radiation for example), you would expect JVP to be increased because of the right heart failure…
well JVP normally drops during inspiration because blood rushes to the lungs but in kussmauls sign, patients with constrictive pericarditis get a paradoxical rise in JVP because the volume restricted right ventricle cannot accomodate the inspiratory increase in venous return by sending it all to the lungs
holosystolic murmur
mitral regurg at the apex
VSD at the left lower sternal border
what can cause a loud P2
pulmonary hypertension
what is the S3 and pericardial knock
S3= reduced wall compliance (maximally dilated) seen in restrictive cardiomyopathy
pericardial knock= sharper more accentuate S3 heard earlier in diastole… due to reduced compliance due to an external force (like constrictive pericarditis)
where do S3 and S4 occur
S4—–S1—-S2—S3—
P) (QRS) (before T) (after T
mid systolic click
MVP
What causes claudication
atherosclerosis of larger arteries
(lipid filled intimal plaques)
pain= ischemia
in thigh= external iliac, or common femoral, or superficial femoral, or profunda femoris
in penis (ED)= aortoiliac atherosclerosis cuts off blood flow to internal pudendal branches of the internal iliac
Calculate dose to maintain a therapeutic steady state plasma conc of a drug (what is the equation)
Maintenance dose= Cpss x CL/ [bioavailability fraction]
Cpss= steady state plasma conc
CL= clearance
bioav=1 for IV drugs
ex= abx is first order kinetics, volume of distribution is 70 L, clearance is 0.5 L/min… how much should be administered every 6 hours to maintain Cpss of 4mg/L?
Maintenance dose= 4mg/L x 0.5 L/min= 2mg/min
but they asked in 6 hour intervals…
2mg/min x 60 min/hr x 6 hrs= 720 mg
what is the equation for half life
Vd x 0.7/CL
Vd= volume of distribution
steady state conc or elimination takes 4-5 half lives
what is the equation for loading dose
Vd x Cpss/ [bioavailability fraction]
in patients with kidney or liver disease, the loading dose is the same but the maintenance dose is decreased
30 yo asian with exertional calf pain and painful foot ulcers develops hypersensitivity to intradermally injected tobacco extract. Whats the pathology to blame?
segmental vasculitis extending into contiguous veins and nerves
Buerger’s disease (thromboangiitis obliterans of smokers)… acute and chronic vasculitis of medium and small arteries, mostly the tibial and radial arteries
symptoms= distal lower extremity vasc insuff… calf/foot/hand claudication, superficial nodular phlebitis, raynauds, severe distal pain even at rest….. later complications= ulcerations and gangrene toes/feet/fingers
presumably a heavy smoker who has thus developed immune hypersensitivity to tobacco smoke
heavy cig smokers under 35 is classic patient (often seen in israel, japan, and india)
tx= stop smoking
Describe the consequences of a lightning injury
lichtenberg figures (erythematous cutaneous marks in a fern leaf pattern) second degree burns
lightening injuries are associated with 25% fatality rate.. 2/3rd die in the first hour due to fatal arrhythmias and resp failure
(>70% with long lasting complications)
fixed and dilated or asymmetric pupils in lightening injury caused by damage to the ANS from the lightening
asses for mechanical trauma and fractures due to rapid heating of surrounding air which causes shock waves that travel through and damage the body
What is the cause of death in a patient with acute MI?
ventricular fibrillation
Vfib is the most frequent mechanism of sudden cardiac death in the first 48 hours after an acute MI and is related to electrical instability due to the lack of perfusion in the ischemic myocardium
describe the morphologic changes to the heart seen in normal aging
decreased LV chamber size particularly apex to base (shortening of the heart all together it looks like)
which causes the septum to acquire a sigmoid shape with the basilar portion bulging into the LVOT
atrophy of the myocardium resulting in increased interstitial connective tissue (often with amyloid deposition)
in cardiomyocytes there is progressive accumulation of cytoplastmic granules with brown lipfuscin pigment (indigestible byproducts of membrane lipid oxidation)
so again in summary: small LV sigmoid septum more connective tissue brown pigment
Polyarteritis nodosa affects what arteries
segmental, transmural, necrotizing inflamm to small and medium arteries of any organ
renal artery involvement is common
PAN spares pulmonary arteries and bronchial arteries (polyarteritis nodosa leaves the lungs alone)
bead like aneurysm formation, especially the mesenteric
cutaneous sx= livedo redticularis and palpable purpura
hypoxia causes what in the pulmonary vasculature vs other organs?
hypoxia causes vasoconstriction in the pulm vessels and causes vasodilation in other organs (hypoxia in the lungs occurs in order to divert blood to better oxygenated segments of the lung)
what metabolites control autoregulation of the heart’s perfusion?
oxygen, adenosine (potent vasodilator), NO
what metabolite controls autoregulation of brain perfusion?
CO2 or pH
what controls autoregulation of kidney perfusion?
myogenic (stretch induced contraction) and tubuloglomerular (macula densa of JGA cells cause vasoconstriction of the afferent arteriole when it senses too much solutes and water) feedback (maintain GFR at a range of BPs)
what controls autoregulation of skeletal muscle perfusion?
lactate (anaerobic states), adenosine (potent vasodiator), potassium (released by contracting muscle and works to increase the amount of blood in vessels when levels are higher)
what controls autoregulation of skin perfusion?
sympathetic stimulation
what is the equation for net filtration pressure?
NFP= [(capillary pressure-interstitial fluid pressure) - (plasma colloid osmotic pressure-intersitial fluid colloid osmotic pressure)]
basically hydrostatic pressure minus oncotic pressure…. then within that, always capillary minus intersitium
What is the equation for net fluid flow?
Net fluid flow= (Net filtration pressure) x (filtration constant for capillary permeability aka Kf)
insults (like toxins, infections, or burns) increase capillary permeability and thus increase the Kf (filtration constant) which causes edema
lymph obstruction increases interstitial oncotic pressure pulling water out of capillaries
aortic arch receptors transmit impulses to the medulla via which nerve? in response to which stimulus?
aortic arch receptors transmit impulses along the vagus nerve to the medulla during high blood pressure (because vagus nerve gives back PNS)
carotid sinus receptors transmit impulses to the medulla via which nerve in response to which stimuli?
carotid sinus receptors transmit impulses along the glossopharyngeal nerve in response to high and low blood pressures (baroreceptors!)
what do brain/central chemoreceptors respond to?
pH and Pco2 (both influenced by arterial CO2)
central chemoreceptors responsible for the cushing reaction (physiological nervous system response to ICP resulting in cushings triad= HTN, resp depression, and bradycardia… due to brain ischemia)…
often seen in terminal stages of acute head injury and may indicate herniation
which receptors are most important in responding to severe hemorrhage?
Baroreceptors
what do peripheral vs central chemoreceptors respond to?
peripheral = low PO2 (<60), high PCO2, and low pH….. central = not sensitive to oxygen
which organ gets the largest share of the systemic CO ?
the liver
which organ gets the highest blood flow per gram of tissue?
the kidney
Where does a Stanford Type B aortic dissection occur?
the descending aorta (with no ascending involvement)
specifically they originate close to the origin of the left subclavian artery (just past the bifurcation of those major three branches off of the aortic arch)
as a reminder, type A originate in the sinotubular junction
these areas specifically because of increased pressure and shearing forces here in patients with severe HTN
both types can propagate distally to the thoracic aorta
describe the symptoms of an obstructed right brachiocephalic (innominate) vein
right sided face and arm swelling
engorgement of subcutaneous veins on the right
the brachiocephalic vein drains the internal jugular vein an the subclavian vein (both on the same side)
both the brachiocephalic veins combine to form the SVC, thus brachiocephalic obstruction causes symptoms of SVC syndrome BUT ONLY ON ONE SIDE of the body
SVC obstruction would be the whole face/neck/chest, and both arms
ANP and BNP are what kind of hormones
peptide hormones
increased when the heart’s walls are stretched
they increase cGMP… dilate the afferent arteriole and constrict the efferent arteriole…. causes increased GFR and natriuresis/diuresis… they also inhibit renin secretion and sodium reabsorption
where is the SA node
in the right atrium near the opening of the SVC (upper left ish area)
the AV node on the other hand is in the RA near the septal cusp of the tricuspid valve (lower right ish area)
giving normal saline to a patient in hypovolemic shock changes what hemodynamic parameter?
giving fluid increases volume and preload
the increased preload stretches the heart and increases end diastolic sarcomere length
according to frank starling, increasing preload causes an increase in stroke volume and cardiac output
CO= SV x HR
what heart abnormality causes bounding pulses (“water-hammer” pulses) and head bobbing
aortic regurg
precordial impulse is hyperdynamic and displaced laterally and downward
bounding pulses= wide pulse pressure (increase in total stroke volume with abrupt distension and rapid falloff of peripheral artery pulses)
head bobbing= “de Musset sign” due to large LV stroke volume being transfered to the head and neck
early diastolic blowing decrescendo murmur
what are the common causes of acquired QT prolongation? (not drugs)
hypokalemia
hypomagnesemia
drugs: class 1A class 3 abx (macrolides, fluoroquinolones) methadone antipsychotics (haloperidol)
what cell are responsible for the fibrous cap seen in atherosclerosis
vascular smooth muscle cells within the intima are stimulated to synthesize extracellular matrix proteins (including mostly collagen, but also some elastin, and proteoglycans) that form the fibrous cap of typical mature atheromas
describe the effects of milrinone (and inamrinone)
(the elephant poster on the wall of the digoxin video)
milrinone is a phosphodiesterase (PDE) 3 enzyme inhibitor occasionally used as an inotropic agen in patients with refractory heart failure due to LV systolic dysfunction
PDE inhibitors decrease the degredation of cAMP, the increased cAMP causes calcium influx into cardiac myocytes and increases cardiac contractility
it also inhibits cAMP breakdown in vascular smooth muscle cells causing systemic arterial and venous dilation…. this decreases BP so be careful in patients with hypotension
(increased inotropy and vasodilation will increase renal blood flow)
why do ACEI cause angioedema
angioedema is subcutaneous swelling in the face, throat, lips, mouth, and genitalia.
side effect of ACEI because of bradykinin (that isnt degraded)
is high cholesterol a bigger risk factor for aortic aneurysm or dissection?
aneurysm>dissection
esp AAA (atherosclerosis also predisposes to aortic aneurysms)
what CV problem is tertiary syphilis a risk factor for?
AAA
tertiary syphilis results in spirochetal endarteritis that affects the vasa vasorum in the adventitia of the ascending thoracic aorta
this weakens the aortic wall and predisoposes to AAA
what is nonbacterial thrombotic endocarditis? (NBTE)
sterile platelet rich thrombi attached to mitral valve leaflets
commonly associated with advanced malignancy (often in mucinous adenocarcinomas…. circulating mucin is procoagulant)
also associated with chronic inflammatory disorders like:
antiphospholipid syndrome
SLE (libman-sacks endocarditis)
DIC in patients with sepsis
NBTE starts with endothelial injury caused by circulating cytokines which triggers platelet deposition (during a hypercoagulable state)
vegetations= bland thrombus with strans of fibrin, immune complexes, and mononuclear cells (white thrombus)
they can be microscopic up to super large (verrucous endocarditis)
most of these are asymptomatic
vegetations from NBTE are more likely to embolize than IE vegetations
what is a cardiac myxoma
the most common primary cardiac cancer in the atria
histo= made of scattered cells in a vascular mucopolysaccharide stroma
what are the cardiac manifestations of systemic sclerosis
cor pulmonale due to pulm artery HTN
pericardial disease
myocardial fibrosis
and conduction system disease
what are the side effects of adenosine
transient flushing burning in the chest (bronchospasm) SOB high grade AC block (and sense of impending doom)
adenosine is the drug of choice for paroxysmal supraventricular tachycardia
10 second adenosine slows conduction through the AV node by hyperpolarizing the nodal pacemaker and conducting cells
this is the chemical stress test drug
what are ADRs of lidocaine and procainamide
lidocaine (class 1B)= neurologic symptoms
procainamide (class 1A)= drug induced lupus syndrome
what are the ADRs of verapamil
(class 4) CCB, most cardioselective of the CCBs
potent neg inotrope
was the old favorite before adenosine
causes constipation and gingival hyperplasia
what are the ADRs of digoxin
positive inotrope and slows conduction through the AV node
causes fatigue blurry vision changes in color perception nausea vomiting diarrhea abdominal pain confusion delirium
free wall rupture s/p transmural MI occurs when?
typically occurs 5-14 days after an acute MI
after inflammatory infiltration and DURING COAGULATIVE NECROSIS
(which weaken the connective tissue)
rupture appears as a slit like tear with preference for the LV due to highter pressures
death due to cardiac tamponade–> profound shock—-> rapid progression to electromechanical dissociation (death)
prior history of MI reduces the risk of rupture because there is already fibrosis (scar) formation and collateral circulation…. likewise LV hypertrophy is protective of rupture
what is the most common cause of sudden death within 2-3 days of MI
ventricular arrhythmias
what makes mitral regurg “functional”
it means that it was due to transient hemodynamic factors causing LV dilation or papillary muscle ischemia rather than a fixed mitral valve lesion (aka reversible by decreasing preload and increasing afterload)
acute LV dilation sufficiently seperates otherwise normal mitral valve leaflets, permitting regurg
the most common anatomical abnormality causing mitral regurg is mitral prolapse (aka myxomatous degeneration)
a fixed anatomic MR would be caused by something like chordae tendineae rupture
what are the potassium sparing diuretics
amiloride
triamterene
spironolactone
or k+ supplements
hyperkalemia can be in patients taking ACEI alone if the patient has renal insuff… otherwise its in patients on an ACEI taking a potassium sparing diuretic
what is indapamide
a thiazide diuretic that blocks NaCl symporters on the distal tubule
why is infarction rare in a normal liver
because of dual blood supply from the portal vein and the hepatic artery
if the hepatic artery becomes occluded the portal venous supply and retrograde flow through accessory vessels is sufficient to sustain the parenchyma
not the case for a transplanted liver because the collateral blood supply is severed during transplantation
rank organ susceptibility to infarction after occlusion of a feeding artery from greatest to least
most likely to infarct:
CNS> myocardium> kidney> spleen> liver
what is salicylism and what causes it
very high doses of aspirin cause salicylism: vertigo tinnitus hearting loss hyperpnea (stimulates resp drive)
the hyperpnea causes resp alkalosis
the salicylate accumulation causes a concurrent metabolic acidosis
what is pioglitazone
a thiazolidinedione
which increases insulin sensitivity in patients with DM2 due to binding of peroxisome proliferator activated receptors
long term use is associated with urinary bladder cancer
what are the risk factors for AAA (below the renal arteries)
>60 yo smoking HTN male family history
leads to oxidative stress, VSMC apoptosis, and CHRONIC TRANSMURAL INFLAMMATION of the aorta
macrophages release matrix metalloproteinases and elastases that degrade extracellular matrix components (elastin, collagen) leading to a weakening and progressive expansion of the aortic wall
also contributing is ischemia of the tunica media and thickening of the intima
remember that a pulsatile central abdominal mass is an aneurysm not a dissection
what is cystic medial necrosis in marfan syndrome
in the aortic media there is replacement of smooth muscle, collagen, and elastic tissue with cystic mucoid spaces
this occuring at the aortic root predisposes them to aortic aneurysm and dissection
no microscopic changes are seen in an acute MI until when
until 4 hours after severe ischemia
then after 4 hours you can see early signs of coagulative necrosis, edema, hemorrhage, and wavy fibers (soon including contraction band necrosis)
describe concentric hypertrophy due to long standing HTN
LV hypertrophy= increased wall thickness (concentric= due to increased afterload) or cavity size (eccentric= remodeling, decreased wall thickening with associated increase in chamber size due to volume overload)
concentric= uniform thickening of the ventricle with narrowing of the cavity
patients may develop diastolic dysfunction and LA enlargement causing CHF
LV enlargement causes LA enlargement not the other way around
LA enlargement would cause pulm problems
most common cause of IE in developed and non developed nations
developed= MVP (for native valve IE)
nondeveloped= ARF
what vessel is occluded in a lateral MI
left circumflex artery (think of lateral as the left side of the heart towards the patient’s back)
lateral means lateral left ventricle
left circumflex comes off the left main coronary artery
what MI is caused by an occluded proximal vs distal LAD artery
LAD supplies the anterior left ventricle and interventricular septum
anterior/septal leads= v1-v4
proximal LAD occlusion will occlude all the leads (v1-v4)
but
distal LAD occlusion spares the septum (v3 and v4 affected only)
where is the MI when the right coronary artery is occluded
right coronary artery supplies the right ventricle and the inferior left ventricle
thus you’ll get an inferior MI (leads 2,3, avF)
what heart problem causes dysphasia to solid foods
LA extrinsic compression of the esophagus
“cardiovascular dysphasia”
Resistance (R)= (viscosity x length)/radius to the fourth power
reducing the flow through an artery by a factor of 16 means what percentage of the radius of the lumen has been reduced?
reduced by 50%
basically 2^4 is 16 so you know its two
and since youre getting smaller, you know the 2 is in the denominator (and thus its divided in half)
what is the cause of death in patients with pulmonary HTN
right heart failure with circulatory collapse and resp failure
how does left heart disease cause pulmonary HTN
due to vasoconstriction due to pulmonary venous congestion
left heart backs up into the lungs
the high pressures cause endothelial damage and capillary leakage of serum proteins in to the interstitium
this leads to decreased production of NO and increased endothelin (vasoconstrictor)
this causes increased vasc tone
over time remodeling of the pulm vasc occurs due to smooth muscle cell proliferation (medial hypertrophy) and collagen deposition (intimal thickening and fibrosis)
(in this case the remodeling isnt as bad as it is in idiopathic PAH so its usually partially reversible if you fix the left heart issue)
remember that although pulm artery pressures are rising due to left heart disease, pulmonary arterial flow remains constant or decreases as HF worsens
which diuretic improves survival
MC receptor antagonists (basically aldosterone receptor antagonists)= spironolactone and eplerenone
these block the deleterious effect of aldosterone on the heart causing regression of myocardial fibrosis and improvement of ventricular remodeling
MC-R antag reduce morbidity and improve survival in patients with CHF and decreased EF
thus they are recommended in addition to standard HF meds (ACEI and beta blockers)
what causes prominent intracytoplasmic granules tinged yellow brown color in the heart
an insoluble pigment composed of lipid polymers and protein complexed phospholipids
lipofuscin is considered a sign of “wear and tear” or aging
this yellow brown finely granular perinuclear pigment is the product of free radical injury and lipid peroxidation
commonly seen in the heart and liver of aging or cachectic malnourished patients
What are other causes of browth pigments
hemosiderin= iron overload
melanin= oxidation product of tyrosine metabolism
what is the mutated gene in HOCM
AD
sarcomere gene single point missense mut (encodes myocardial contractile proteins)
ex:
beta myosin heavy chain
myosin binding protein C
mutations in these genes cause what diseases?
dystrophin
fibrillin 1
IK membrane potassium channel
transthyretin
dystrophin= x linked familial dilated cardiomyopathy and also skeletal myopathies (duchenne and becker muscular dystrophy… both have CV involvement)
fibrillin 1= marfan syndrome
IK membrane potassium channel= congenital long QT syndrome
transthyretin= hereditary cardiac amyloidosis
what kind of damage to the mitral valve predisposes IE
valvular abnormalities: ARF causing rheumatic heart disease MVP prosthetic valves cong heart disease
immigrant with hx heart disease= rheumatic heart disease
this causes degeneration of the mitral valve due to chronic valvular inflammation and scarring
remember that rupture of chordae tendineae is a complication of endocarditis or MI, not a risk factor
what is the initial process in the pathogenesis of IE
disruption of normal endocardial surface (mostly at areas of maximal turbulence to blood flow… aka where there was previous damage)
next comes platelet and fibrin deposition forming a sterile fibrin platelet nidus (nidus= site of deposition)
bacteria colonize the sterile nidus which activates coagulation
what is kallikrein?
kallikrein activates bradykinin
activation of the kallikrein-kinin system (KKS) plays a major inflammatory role in the lung (on epithelial cells)
(the role of KKS in the plasma is unknown)
what is collapsing pressure and what is the equation to calculate it?
the pressure at which a tube or vessel deforms due to pressure from outside the tube
collapsing pressure= 2 x (surface)tension/(alveolar)radius
how do nitrates and thiosulfate treat cyanide poisoning
nitrates oxidizes hemoglobin into methemoglobin
methemoglobin binds cyanide
(allowing cytochrome oxidase to function… this is part of the ETC)
after nitrates give thiosulfate to bind the cyanide-methemoglobin complexes to form thiocyanate which can be renally excreted
how do you treat methemoglobinemia
methylene blue
remeber METHemoglonin is treated with METHylene blue
what vessel is occluded in 90% of patients with an inferior MI
the posteroinferior wall of the left ventricle is supplied by the posterior descending artery (Right dominant heart this comes off of the right coronary artery)
the right coronary artery also supplies the SA node too (will cause bradycardia and hypotension)
adding what drug to a statin increases the risk of severe myopathy
statins and fibrates (esp gemfibrozil)
gemfibrozil and fenofibrate impairs the hepatic clearance of statins leading to excessive blood levels
also possible with concurrent use with niacin or ezetimibe but not as much as with fibrates
statin assoc myopathy= mild muscular pain (resolves when stopping statin)… severe myopathy= elevated creatine kinase and occasional rhabdomyolysis
statins also cause hepatitis
what affect do bile acid sequestrants have on statins
bile acid sequestrants (like cholestyramine) reduce the GI absorption of statins
what are the ADRs of niacin
niacin causes flushing, hyperglycemia, and hepatotoxicity
what is the Beck triad of symptoms in cardiac tamponade
hypotension
elevated jugular venous pressure
muffled heart sounds
causes late diastolic collapse of the RA due to displacement of the pericardial fluid with ventricular expansion
(a large RV in a confined space causes fluid to move up and take the space that the RA used to)
also get pulsus paradoxus= exaggerated drop in systolic blood pressure during inspiration (“drop in pulse amplitude during inspiration”)…
inspiration= increased venous return causing the septum to bow into the LV (thus also, the LV will now have lower preload and stroke volume) aka decreased systolic pulse pressure during inspiration
what is a “beat to beat variation in the pulse amplitude” describing
pulsus alternans
due to a change in systolic BP
seen in severe LV dysfunction
electrical alternans= beat to beat variation in the QRS complex amplitude
seen in large pericardial effusion or cardiac tamponade and is due to the swinging motion of the heart in the pericardial fluid
what is a “pulse with 2 distinct peaks” referring to
a dicrotic pulse (one peak for systole and another for diastole)
it is due to an accentuated diastolic dicrotic wave after the dicrotic notch (of the aortic pressure wave)
seen in patients with severe systolic dysfunction and high systemic arterial resistance
what is a “rapidly rising pulse with high amplitude” describing
a hyperkinetic pulse
it is due to the rapid ejection of a large stroke volume against a low afterload
occurs with aortic regurg and high output conditions (like thyrotoxicosis or AV fistula)
what is a “slow rising low amplitude pulse” describing
causes pulsus parvus et tardus (a palpable pulse as described with diminished stroke volume and prolonged ejection time)
due to a fixed LV outflow tract obstruction (aortic stenosis)
what are the different causes of pulsus paradoxus
exaggerated drop (>10mmHg) in systolic BP with inspiration
seen in: cardiac tamponade severe asthma COPD hypovolemic shock constrictive pericarditis
what is norepi extravasation?
when norepi is being infused into a vein and the IV site becomes cold, hard, and pale (showing blanching, induriation, and pallor)
basically what happens is the norepi is leaking and causing intense alpha 1 vasoconstriction and is leading to local tissue necrosis
you can prevent the necrosis with an alpha blocker injection (give antidote= 10-15cc of sodium chloride solution with 5-10mg of PHENTOLAMINE mesylate with a syringe and fine hypodermic needle)
must be given within 12 hours of extravasation
norepi alpha1>alpha2>beta1
use norepi for shock and severe hypotension (but it causes a reflex bradycardia)
when do you use epinephrine
beta> alpha
use for: anaphylaxis cardiac arrest open angle glaucoma asthma/broncospasms hypotension
when do you use:
midodrine
phenylephrine
clonidine/alpha methyldopa
isoproterenol
dopamine
fenoldopam
bromocriptine
dubutamine
metaproterenol/albuterol/salmeterol
ritodrine/terbutaline
midodrine (alpha 1 agonist) for orthostatic hypotension
phenylephrine (alpha 1>alpha 2) for wide angle glaucoma, pupillary dilation, vasoconstriction, nasal decongestion
clonidine/alpha methldopa (central acting alpha agonist, decreases central adrenergic outflow) used for HTN, does not decrease blood flow to the kidney
isoproterenol (beta 1=beta 2) used for heart block
dopamine (low dose vasodilation and natriuresis D1=D2… medium dose tachycardia beta 1…. high dose vasoconstriction alpha 1, inotropic and chronotropic) for shock and increasing renal perfusion, and heart failure
fenoldopam (D1 agonst) for HTN
bromocriptine (D2 agonist) for parkinsons disease and prolactinemia
dobutamine (beta 1>beta 2 and positive inotrope) for cardiogenic shock, acute HF, and cardiac stress testing
metaproterenol/albuterol/salmeterol (beta 2 agonist) for acute asthma and long term asthma (sal)
ritodrine/terbutaline (beta 2 agonist) for reduction of premature uterine contractions
early diastolic murmur
aortic regurg
in developed nations the most common cause is aortic root dilation (best heard on the right) or bicuspid aortic valve
the accompanying fatigue and DOE are likely due to left heart failure
what murmur radiates to the axilla
mitral regurg
some blood from the LV is pumped forward (forward stroke volume) and some is forced backwards by the incompetent mitral valve (regurg strok volume)
the forward flowing amount of blood is determined by LV afterload (thus decreasing afterload will increase forward flow)… you can achieve this with an arterial vasodilator (which will also help with HF symptoms)
main tx= surgery though
decreasing heart rate does what to preload to the LV
increases preload because there is more time in diastole for the ventricle to fill now and thus the stroke volume will also increase
what are the absolute contraindications for OCPs
- history of clot
- an estrogen dependent tumor
- women over 35 who smoke heavily
- hypertriglyceridemia
- decompensated or active liver disease (impairs steroid metabolism)
- pregnancy
what are the class 1B antiarrhythmics
lidocaine
mexiletine
great for treating ischemia induced ventricular arrhythmias because the weak binding and rapid dissociation allows rapid dissociation of the drug from the normal tissues
the strongest binders and slowest dissociators have high use dependence and are great for terminating tachyarrhythmias
(conduction delay side effect can promote arrhythmias)
in a free wall rupture in the 5-14 days s/p MI what is the cause of death
free wall rupture causes hemopericardium and cardiac tamponade
they get PROFOUND HPOTENSION AND SHOCK with rapid progression to pulseless electrical activity and death
describe the presentation of a cardiac atrial myxoma (primary heart cancer)
constitutional symptoms of cancer (myxomas produce a large amount of IL6)
mid diastolic rumbling murmur at the apex
positional dyspnea
large pedunculated mass in the LA
80% occur in the LA
histo= scattered cells within a mucopolysaccharide stroma with [abnormal blood vessels and hemorrhaging= due to the large amounts of vascular endothelial growth factor produced by myxomas… this is seen as hemosiderin deposition which is brown]… these tumors are friable
symptoms are due to valve obstruction by the tumor
what does fungal endocarditis look like on histo
coarse filamented branching septate hyphae
patients with acute myeloid leukemia (AML) present with what symptoms typically
symptoms of pancytopenia
anemia
neutropenia
thrombocytopenia
aka weakness easy fatigability infections ecchymoses epistaxis
coronary dominance is determined by the artery that supplies which branch?
the posterior descending interventricular artery
right dom= right coronary artery (70%)
left dom= left circumflex artery (10%)
codominant= both (20%)
which artery branch supplies the AV node
the AV nodal artery most often arises from the dominant coronary artery
(because the AV node gets blood from the posterior descending interventricular artery)
describe the pain of acute pericarditis
sharp and pleurtitic
decreases with sitting up and leaning forward
most common type is fibrinous or serofibrinous pericarditis
physical exam= pericardial friction rub (high pitched, leathery, and scratchy)
causes: MI ARF uremia viral infection (causing exudate)
what is kussmaul’s sign
paradoxical increase in JVP with inspiration
often seen in chronic constrictive pericarditis
what is a pericardial knock
brief, high freq, precordial sound heard shortly after S2 in patients with constrictive chronic pericarditis
what is the most common cause of renal infarction
blood clots from the left heart
What is migratory thrombophlebitis associated with
cancer
hypercoagulability is common to paraneoplastic syndrome seen in visceral adenocarcinomas of the pancreas, colon, and lung
adenocarcinomas produce a thromboplastin like substance capable of causing chronic intravascular coagulations that can disseminate and tend to migrate (=hypercoagulability)
migratory superficial thrombophlebitis = “trousseau syndrome” … the man diagnosed his own visceral cancer after discovering it!… it causes superficial venous thromboses that appear in one site, resolve and recur in another site
[same trousseau that named the arm BP spasm sign associated with hypocalcemia]
is celiac sprue associated with bleeding or clotting
bleeding because malabsorption results in vit k def and def of vit k clotting factors
what is disseminated chlamydia infection associated with
reactive arthritis
how do you calculate cardiac output via the Fick principle
basic is
CO= SV x HR
with Fick principle: (using a swan ganz catheter)
CO= rate oc O2 consumption/arteriovenous O2 content difference
consumption determined with an oxygen meter by measuring the rate of disappearance of oxygen in exhaled air
how do you calculate the blood oxygen content
blood O2 content= (O2 binding capacity x % saturation) + dissolved O2
what are the two important congenital long QT syndromes
- Jervell and Lange Nielsen syndrome
AR with neurosensory deafness - Romano ward syndrome
AD
no deafness
both predispose torsades, syncope, and sudden cardiac death
what is the embryologic origin of the PDA
PDA comems from the 6th aortic arch
PDA presenting with failure to thrive, SOB, and exerise intolerance in a 4 yo boy with continuous murmur, bounding peripheral pulses and palable thrill
symptoms reflect a left to right shunt that is causing LV volume overload and symptoms of heart failure (the failure to thrive and resp distress)
the murmur is machine like but they didnt mention that and its accompanied by a palpable thrill due to turbulent blood flow through the PDA
tx:
premie infants= meds (PGE2 synthesis inhibitors- indomethacin)
older patients= surgical ligation or percutaneous ODA occlusion
refresh up on the aortic arch vasculature derivatives real quick
1= maxillary artery
2= hyoid artery and stapedial artery
3= common carotid artery and proximal internal carotid artery
4= aortic arch (on left) and proximal right subclavian (on the right)
6= proximal pulmonary arteries and ductus arteriosus (on left)
what is the most common cause of primary MVP
most commonly sporadic defects in the mitral valve connective tissue proteins
characterized by myxomatous degeneration (pathologic deterioration of the connective tissue) of the leaflets and chordae tendineae
what is the most common cause of secondary MVP
associated with inherited connective tissue disorders
marfans
ehlers danlos syndrome
osteogenesis imperfecta
remember that heart valves are made of connective tissue! (no muscle)
why does end expiration exaggerate the S3 heart sound in the left lateral decubitus position
S3 and S4 (LV gallops) are best heard with the bell at the apex in the left lateral decubitus position
at end expiration the sound is louder because lung volume is decreased which brings the heart closer to the chest wall
what disease causes vegetations to the mitral valve on BOTH sides of the valve leaflets
SLE
women of childbearing age
immune complex mediated injury
CV manifestations:
accelerated atherosclerosis
vasculitis of small arteries and arterioles
fibrinoid necrosis in any tissue
verrucuous (libman sacks) endocarditis (thick valves with sterile vegetations on both sides)
renal involvement (Diffuse proliferative glomerularnephrITIS)… diffuse thickening of glomerular capillary walls with “wire loop” immune complex deposition
what is another name for eosinophilic granulomatosis with polyangiitis
churg strauss syndrome
small vessels
necrotizing vasculitis
allergic rhinitis, asthma, and peripheral eosinophilia
what is another name for granulomatosis with polyangiitis
wegener granulomatosis
small vessels
necrotizing vasculitis
upper resp symptoms, sinusitis, otitis media and lower resp, shortness of breath, hemoptysis and renal disease
but! the wegener GPA renal disease is focal necrotizing crescentic glomerulonephritis
in a 3 lead pacemaker, how do they get the third lead into the left ventricle
transvenously passing the lead from the right atrium into the coronary sinus (the atrioventricular groove on the posterior heart) and advancing it into one of the lateral venous tributaries to get to the LV
what causes hereditary PAH
PAH is mean pulm artery BP >25 at rest
due to an inactivating mutation of BMPR2
AD with variable penetrance
2 hit hypothesis: predisposition for dysfunctional endothelial and smooth muscle cell proliferation
a second insult (infection, drugs, ion channels defects) activates the disease
increased endothelin (vasoconstrictor) decreased NO (dilator) decreased prostacyclin (dilator and platelet inhibitor)
thus hereditary PAH has VSMC proliferation, intimal thickening and fibrosis, increased vasc resistance, and pulm HTN
in an atherosclerotic plaque what is the stimuli for the cellular components to come in
PLATELETS
endothelial dysfunction promotes:
platelet adhesion/aggregation
growth factors
cytokines
These promote migration of smooth muscle cells from the media to the intima to proliferate:
PDGF (platelet derived growth factor) from platelets that have locally adhered
platelet’s TGF beta (chemotactic for SMCs)
dysfunctional endothelial cells
infiltrating mactophages
the vascular endothelium secretes which substance to inhibit platelet aggregation
prostacyclin
(prostaglandin I 2) which is in the camily of eicosanoids (arachidonic acid derivatives which act as local hormones)
prostacyclin inhibits platelet aggregation and adhesion to the vascular endothelium…. it also vasodilates, increases permeability, and attracts leukocytes
thromboxane A2 is a prostaglandin that does the opposite (inhances aggregation and vasoconstricts)
damaged endothelial cells are prone to clots because they lose the ability to synthesize prostacyclin
synthetic prostacyclin is used to treat pulm HTN, peripheral vasc disease, and raynaud syndrome
what would you suspect if a patient came in with progressive onset of HF in the setting of a recent viral infection? (aka recent fever, runny nose, and myalgia)
suspect dilated cardiomyopathy (viral injury and autoimmune reaction to virally altered myocytes)caused by viral myocarditis
dilation and enlargement= eccentric hypertrophy
other causes of dilated cardiomyopathy: genetics toxicity (alcohol) pregnancy (peripartum) hemochromatosis
what controls the increase in cardiac output in low exercise vs high levels of exercise
low= mechanoreceptors and chemoreceptors increase SNS
high= HR
in exercise, does the overal systemic vascular resistance go up or down
down
due to substantial arteriolar vasodilation in active skeletal muscles mediated by the local release of adenosine, potassium ATP, CO2, and lactate (thats why there is only a modest increase in blood pressure)
during strenuous activity the muscles can recieve up to 85% of the total CO
what are common symptoms and lab findings in SLE
acute pericarditis
facial rash
proteinuria
clinical: constitutional symptoms arthritis butterfly rash and photosensitivity serositis clotting CNS
labs: blood changes decreased complement (3 and 4) ANA ab (sensitive) anti DNA ab anti SM ab (specific) kidney changes
SLE also causes pericardial effusion, verrucous (libman sacks) endocarditis, and increased risk of CAD
which AR does norepi not effect
beta 2
what cell change is directly caused by norepi therapy
cAMP in cardiac muscle cells
alpha 1 vasoconstriction via the IP3 pathway
beta 1 inotropy conduction and chronotropy due to Gs pathway
(with baroreceptor mediated reflex bradycardia) thus HR is unchanged or decreases
what receptors do each of the AR work on
alpha 1 works on IP3>Ca2+>DAG
alpha 2 decreases cAMP
(decrease release of norepi and insulin)
beta 1 increases cAMP
beta 2 increases CAMP (bronchodilation and vasodilation)
describe these drugs:
statin
ezetimibe
bile acid sequestrants
niacin
fibrates
fish oil (omega 3 FA)
statins cause liver toxicity and muscle toxicity (do LFTs before starting… routine monitoring only if liver injury [fatigue, malaise, anorexia])
ezetimibe decreases cholesterol absorption and causes hepatotoxicity if given with statins
BAS prevent bile acid reabsorption and cause nausea, bloating, cramping, and malabsorption of other drugs and fat vitamins
niacin decreases FA release, VLDL synthesis, and HDL clearance and causes flushing, itching, liver toxicity, and gout
fibrates activated PPAR alpha and decrease VLDL synthesis… they decrease TG the most and cause muscle toxicity and gallstones
fish oil decreases VLDL synthesis and apo B synthesis and causes a fishy taste
what conditions present with isolated high TG
LPL def familial hyperTG (heterozygous) chylomicronemia (homozygous)
what do ketoconazole and aminoglutethimide inhibit
adrenal enzyme inhibitors
what is the treatment for digitoxin toxicity
anti digoxin ab fragments
severe toxicity presents with life threatening arrhythmias and end organ dysfunction
where does nitroglycerin work
large veins
(the chemical structure is shown and there are three branches with NO2 at the end of each one)
nitroglycerin decreases preload
(decreases ventricular wall stress and thus oxygen demand)
vasoactive anti HTN meds work where
small arteries and arterioles
such as CCBs and alpha 1 blockers
varicose veins can lead to what complications?
complications from poor blood flow:
skin ulcerations (over medial malleolus is common) painful clots stasis dermatitis poor wound healing superficial infections
claudication on the other hand is an issue of the arteries… you dont get DVTs cause varicose veins are superficial
what is phlegmasia alba dolens
painful white leg “milk leg”
consequence of iliofemoral venous thrombosis occuring in peripartum women
pregnancy predisposes DVTs because of pressure on the deep pelvic pains producing venous stasis and hypercoagulability
where is ANP produced and how is it related to neprilysin
ANP is secreted by atrial cardiomyocytes
neprilysin is a metalloprotease that inactivates several peptide hormones like bradykinin, glucagon, enkephalins, and natriuretic peptides (ANP/BNP)
drugs can be given to inhibit neprilysin (like sucabitril) to prevent degredation of ANP)
ANP (stimulates cGMP):
dilates afferent arterioles in the kidney, inhibits renin secretion, limits sodium reabsorption, restricts aldosterone secretion, vasodilates, increases permability, decreases blood volume
which complication do you avoid in developing countries by giving abx to patients with GAS pharyngitis
prevents ARF
(and thus need for cardiac surgery)… ARF is the most common cause of acquired valvular heart disease and CV death in developing countries
though though post strep glomerulonephritis is a consequence of GAS infection, early abx have not been shown to reduce the risk of PSGN
(have been shown to prevent ARF)
Can beta blockers be used in an acute MI
yes
they reduce HR
reduce CO
reduce myocardial oxygen demand
they reduce short term morbidity
minimize the infarct size
improve long term survival
contraindications=
bradycardia or heart block
hypotension
overt heart failure (pulm edema)
avoid beta blockers that are non cardioselective (propranolol, nadolol) becaue they cause bronchospasm in patients with lung problems
which are the cardioselective beta blockers
predominant actions on beta 1 receptors
metoprolol
atenolol
bisoprolol
nebivolol
may also use combined beta and alpha receptor blockers like carvedilol and labetalol in patients with lung diseases
(just not the noncardioselective ones)
what can a cardiac catheterization hemodynamic profile show
was given one where the bottom of the aorta line is low and close ish to the LV bottom line (and I had to remember what normal looked like)
basically it showed a wide pulse pressure in the aorta, loss of the dicrotic notch
this abnormal profile plus the question stem (including fatige, DOE, murmur best heard when leaning foward) was hinting at the patient having aortic regurg
aortic regurg is loudest right when the aortic valve closes
in relation to pericarditis, what does exacerbation with swallowing and radiation to the neck suggest
exacerbation with swallowing= posterior pericardium is involved
radiation to the neck= inferior pericardium is involved because it is adjacent to the phrenic nerve that supplies the diaphragm
pericarditis can be a complication in 10-20$ of post MI patients
its usually localized over the necrotic myocardium
it is short lived and goes away within 1-3 days of aspirin therapy
how do you treat Dresslers syndrome
autoimmune reaction to the pericardium and serosal surfaces weeks to months after an MI
treat with
aspirin
NSAIDS
glucocorticoids
what is josten’s mneumonic for remebering what AR are what receptor type
for muscarinic and AR
odd numbers= Gq
even numbers= Gi
all beta (1,2,3) = Gs
endocardial thickening and fibrosis of the tricuspid and pulmonary valves are characteristic of what (leads to tricuspid regurg)
the serotonin of carcinoid heart disease
(neuroendocrine tumor that is well differentiated, found in the small intestine and colon, and metastasizes to the liver)
the secrete serotonin*
histamine
and vasoactive intestinal peptide
(these are all metabolized in the liver thus the liver mets)
results in right heart failure
carcinoid syndrome causes:
flushing
watery diarrhea
bronchospasm/wheezing
diagnosis via 5-HIAA (5-hydroxyindoleacetic acid)… this is the end product of serotonin metabolism
what do you measure to detect tumors that secrete epi and norepi (detect neuroblastoma and other tumors of neural crest origin)
vanillylmandelic acid
what causes the commisures on the heart valves to fuse
chronic rhematic fever
results in mitral stenosis (can precipitate atrial fibrillation or atrial mural thromboses)
mid diastolic murmur with an early diastolic opening snap
tertiary syphilis causes what heart problems
aortitis
aortic aneurysm
aortic regurg
what is the patway to get to the retinal artery? (RAO)
internal carotid (atherosclerosis)>ophthalmic artery>retinal artery
