UW Notes - 7 - Cardiology Arranged

CVS EMBRYOLOGY
274
❖ Cardiac looping
❖ Embryological abnormalities:
- Failure of apoptosis → syndactyly
- Failure of fusion → hypospadias
- Failure of obliteration → branchial cleft cyst
- Failure of proliferation of endocardial cushion → membranous VSD
- Failure of conotruncal septation → Truncus arteriosus
❖ Atria
❖ Outflow Tract Formation
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❖ Aortic arch derivatives
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❖ Embryonic circulation
❖ How you can diagnose paradoxical (cryptogenic) stroke:

- It can evaluated by use of echo with bubble study: agitated saline (saline +
air) is injected through veins → normally you should see the air bubbles in
the right heart, if bubbles appear on the left side = positive bubble test)
- positive test = existing shunt between Rt. & lt. heart → mostly PFO, less
ASD
2
❖ Paradoxical embolism:
• Can occur in ASD, VSD, PFO, large pulmonary AV malformation
• ASD: fixed splitting of S2, functional PS, TS
3
CVS ANATOMY
277
❖ Anatomy of the heart & Trans-Esophageal ECHO (TEE)
❖ What are the structures best visualized by Trans Esophageal ECHO, anteriorly
& posteriorly?
- Anterior → LA, atrial septum, mitral valve
- Posterior → descending aorta
❖ Borders of the heart in CXR:
4
❖ Penetrating from front
- Aortic arch lie behind sternum >>> rare injury if stab
- Penetrating stab in the 2nd intercostal space left sternal >> Pulmonary
trunk could be injured.
- Penetrating stab in the mid- and lower left sternal border >> right ventricle
injury + pneumothorax (pleural injury … not lung injury)
❖ Penetrating from back
- Penetrating stab to the back immediately to the right of vertebral column
>> injures IVC
- Penetrating stab to the back immediately to the left of vertebral column >>
injures descending aorta
❖ Cardiac Anatomy in Normal Aging
❖ Complication of cannulation of CFA above the inguinal ligament: injury to the

posterior wall cause retorpritoneal hematoma which is not controllable by
external compression (the CFA lies beneath the peritoneum)
❖ Aortic dissection:
- Stanford A: flap originates in the sinotubular junction (in the proximal part
of the ascending Aorta before the origin of the brachiocephalic artery)
- Stanford B: flap originates close to the origin of the left subclavian artery
- Swollen arm + swollen face on one side>> unilateral brachiocephalic vein
obs.
- Swollen arm + swollen face on both sides>> SVC obstruction.
- Swollen arm alone >> axillary or subclavian vein obs.
❖ What is the origin of the AV nodal artery? It usually arise from the dominant
artery either RCA & LCX
❖ Inferior surface of the heart :

• Formed by 2/3 LV & 1/3 RV separated by posterior inter ventricular
groove.
• As most individuals are right dominance → most of inferior surface
supplied by RCA
5
❖ Auto-regulation of coronary blood flow:
• the most important factors are NO, adenosine
• Adenosine → the most important in regulating small coronary arterioles,
it is byproduct of ATP metabolism
• NO → the most important in regulating flow in large arteries, pre-arteriolar
vessels. It is produced in response to the mentioned stimualtion
❖ To maintain the blood flow inside the circulation, the arterial flow must be
equal to venous flow, exception is bronchial circulation (bronchial circuit), <
5% of total circulation
❖ Mention the blood supply of the papillary muscles:

 Anterolateral muscle (dual blood supply): LAD & LCX
 Posteromedial papillary muscle → PDA: right dominant circulation →
RCA, left dominant circulation → LCX
 Because Posteromedial muscle depend on single blood supply, it is most
likely to be ischemic & rupture
❖ SA node :
o Site of earliest electric activity in the normal sinus rhythm
o Compact subepicardial structure → specialized pacemaker, site at the
junction of SCV with RA
❖ Atrial fibrillation
- If atrial fibrillation is not permanent (occur in attacks and recurrent) >>
radiofrequency ablation at the pulmonary vein ostia in the left atrium can
be used (pulmonary vein isolation)
- If AV node fail to control the ventricular rate in permanent Atrial
fibrillation >> radiofrequency ablation of the AV node is done.
- Site of AV node: endocardial surface of the RA near the insertion of the
septal leaflet of the tricuspid valve & orifice of the coronary sinus
- Atrial fibrillation >> systemic thromboembolism … the most common site
of thrombus formation is the left atrial appendage
❖ Site of ablation in Atrial flutter: the isthmus between IVC & tricuspid annulus
❖ To access the left side of the heart, there are 2 approaches:

a- from femoral or radial arteries >> aorta >> left side of heart
b- from femoral vein >> IVC >> right atrium >> puncture the interatrial
6
septum at the fossa ovalis >> reach left atrium (puncture is small and
heals spontaneously).
❖ Biventricular pacemaker leads:
• They are either have two or 3 leads
• First two leads are put in the right atrium & right ventricle through left
subclavian vein traversing SVC and reach the right sided chambers.
• The 3rd lead (left ventricular lead) is more difficult → reach to the LV
through RA → coronary sinus (in atrio-ventricular groove) and put
the lead to any lateral venous tributary
❖
❖ Coronary blood flow and its difference from other muscles:
7
o Blood flow is mainly during diastole:
▪ LV → severe pressure (130/10), severe ↓↓ in dyastolic flow to
myocardium
▪ RV → much lower pressure (25/5), relatively constant blood flow
throughout cardiac cycle
o Very high oxygen extraction ratio → resting myocardium extract 60 – 75%
from arterial O2 → so the venous return of heart “coronary sinus”
is the most deoxygenated blood in body
o ↑↑ myocardial O2 needs can only be achieved by ↑↑ coronary blood flow
(by adenosine, NO2) as it has already max. O2 extraction
 Prolonged QT interval is mainly due to repolarization defect → prolonged
T-wave, and slowed repolarization
❖ Mention the main limiting factor of myocardium perfusion:
• During systole, due to ↑↑ Tension & pressure > aortic pressure → no
coronary blood flow during systole
• Main coronary blood supply occurs during diastole, ↑↑ HR will ↓↓
diastole time → ↓↓ time available for max. coronary blood flow
❖ Coronary grafts :
o Occlusion of LAD only ➔ the best graft is left internal mammary
artery → superior patency rate
o Multiple occlusion or non-LAD ➔ GSV is usually used
▪ Anatomy of GSV : 3-4 cm infero-lateral to the pubic tubercle,
access is done from medial leg or at femoral triangle
▪ Deep circumflex iliac vessels → parallel & superior to the
inguinal ligament
❖ Subclavian steal syndrome:

• Due to severe occlusion / stenosis in subclavian artey proximal to the origin
of the vertebral artery.
• The ipsilateral subclavian artery will steal the blood form the contralateral
vertebral artery (away from the brain stem)
• Asymptomatic, but may cause arm ischemia, vertebral insufficiency
with reversal of flow in the ipsilateral vertebral artery.
• SBP in the brachial artery is diagnostic, big difference between the two
sides.
8
❖ Causes of coronary sinus dilatation seen on Echo:
1) Pulmonary hypertension
2) TAPVD
3) Persistent left SVC (drain into coronary sinus)
9
CVS PHYSIOLOGY
278
❖ Fick’ principle for COP measurement:
• Rate of O2 consumption = COP X (A-V O2 content)
• Used to determine COP using Swan Ganz catheter
• Arterial O2 content → ABG, Venous O2 content → catheter in PA.
• Rate of O2 consumption → detected by O2 meter by easuring rate of
disappearance of O2 in exhaled air
279
❖ Cardiovascular Effects of Adrenergic Drugs
10
280
❖ Non-Drug Variables and Effects – maximum velocity of shortening
- when a skeletal muscle contracts, its maximum velocity of shortening is
indirectly/inversely proportional to the afterload attached to the fiber,
- maximal contractile shortening velocity increases as afterload decreases,
- whereas the greatest velocity of shortening occurs when there is no
afterload
281
• except at their ostia
❖ Which change in
• Anaphylaxis, as VR ↓↓, COP ↑↑ due to ↓↓ TPR & to maintain BP
11
❖ Which change in
• Chronic anemia lead to mildly ↑↑ VR (due t low blood viscosity), ↑↑ COP
due to ↓↓ TPR & to meet the needed COP
• In such curves, change sin TPR & blood volume affect both curves
❖ Cardiac & vascular function curves in Arteriovenous Fistula –

acute (left) and chronic (right)
• Acute AV fistula: ↑↑ COP & ↓↓ TPR, but no ↑↑ of MAP initially. By time

↑↑ sympathetic outflow → ↑↑ contractility, vascular tone → ↑↑ MAP
12
• Chronic AV fistula ➔ ↑↑ COP (↑ height of CO curve), ↓↓ TPR (↑↑ CO &
VR curve), ↑↑ MAP (↑↑ VR on X-axis (PSFP ))
❖ During exercise; ↑↑ sympathetic flow→ vasoconstriction of BV except for the
exercising muscles → shift of the blood to the muscles, blood (↑VR), but TPR ↓
due to vasodilatation (in response to local metabolites
282
❖ Pressure-Volume Loop
13
❖ Diastolic heart failure:
• Normal EF, normal LVEDV with ↑↑ LVEDP
• LVEDP determined by blood volume in LV & compliance
• Caused by ↓↓ compliance (e.g. amyloidosis), ↓↓ relaxation (ischemia)
• Notice the difference between ↑↑ preload curve & ↑↑ contractility curve
❖ Diastolic dysfunction:
• Due to ↓↓ compliance of the ventricle == ↑↑ pressure inside the ventricle for given
volume → shift the pressure volume curve to the upper side.
• ↓↓ compliance → ↑↑ end diastolic pressure at same level of end diastolic volume
➔ higher LVED pressure → transmit the pressure to the lug cause pulmonary
edema
❖ ↑↑ preload, ↓↓ after load >>> AV fistula
❖ Effect of nitroperruside on flow-loop curve:
14
❖ Cardiac Cycle
- In tracing the cardiac cycle, first detect where is the systole & diastole, plot
the vales that open and closed then answer
15
16
❖ Tracing of aortic stenosis (how to detect the pathology in left heart
catheterization)
1) Determine the points where the mitral & aortic valve open & close
2) Determine where is the systole & diastole
3) Notice the pressure of the LV, aorta (normally SBP at both are equal)
❖ Describe the normal finding of aging process in the heart:

• ↓↓ LV chamber size, especially apex to base dimensions
• Sigmoid shape of the IVS (due to shortened heart) → with basilar
portion of the IVS bulge into the LVOT
• ↑↑ interstitial CT & amyloid deposition
• ↑↑ Lipofuschion pigments
• Enlarged LA & aortic root
284
❖ What are the physiological changes occur in response to standing:
1) ↓↓ VR to the heart → ↓↓ ventricular filling → ↓↓ COP
2) ↓↓ BP → compensatory baroreceptor reflex → ↑↑ sympathetic tone → ↑↑
HR, vasoconstriction, contractility
4 phases of Valsalva:
1.) Phase 1: onset of straining with increased intrathoracic pressure, heart rate
doesn’t change, but BP rises,
2.) Phase 2: decreased venous return and consequent reduction in stroke volume
and pulse pressure as straining continues, HR increases and BP drops,
3.) Phase 3: release of straining decreases intrathoracic pressure and normalizes
pulmonary blood flow,
4.) Phase 4: BP overshoots in normal heart with return of heart rate to baseline,
Phase 2 used to distinguish fixed LV outflow obstruction (e.g. valvular Aortic Stenosis),
from dynamic obstruction (e.g. Hypertrophic Cardiomyopathy, Mitral Valve
Prolapse): valvular Aortic Stenosis murmurs decrease due to decreased venous
return and blood flow through the heart, however this decreased blood flow means
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less room in the LV, so Mitral Valve Prolapse (MVP) and Hypertrophic
Cardiomyopathy (HOCM) murmurs get louder, with earlier onset of the
click/murmur in MVP,
Phase 4 can be used to distinguish right-sided murmurs (return to normal immediately
after stopping Valsalva) from left-sided murmurs (require 5-10 cycles to return to
normal)
❖ Why patients with MVP on squatting lead to disappearance of the murmur,
late click
18
285
❖ Why AF is more prevalent in AS?
• AS cause LV concentric hypertrophy → ↑↑ LV EDP → this pressure will be
transmitted to the LA → dilatation of the LA → more AF will occur in
response to this dilatation.
• AF indicate more severe AS
❖ Why AF in cases of severe aortic stenosis lead inevitably to acute LV failure?
• Patients with severe AS can ↑↑ LV wall thickness → ↓↓ LV complicance &
impaired end diastolic volume, making the atrial contraction related filling
of the LV is a good proportion of the LV EDV → so in AF, loss of this atrial
contraction → rapid loss of the LV preload → more ↓↓ COP → acute failure
❖ Oscaltatory findings in AS (other than murmur) : ↓↓ S2, ↑↑ S4
❖ Holosystolic murmurs are TR, MR, VSD;

 TR murmur → ↑↑ with inspiration (Carvallo sign), best heard at left sternal
border.
 Carvallo sign: during inspiration → VR to the lung ↑↑ with ↑↑ RV VR, blood
is pooled inside the lung so subsequent ↓↓ VR in the LV, occur only with
right sided valve lesions.
❖ Pathological changes that lead to formation of MVP: proliferation of spongiosa

of the valve leaflets, fragmentation of the elastic fibers, ↑↑
mucopolysaccharides, type III collagen deposits
❖ Clinical findings of chronic aortic regurge:

• Head bobbing (de Musset sign) → due to forceful pulsations in the intra-
cranial arteries
• Abrupt distension & collapse of the carotid arteries (Corrigan sign)
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• Pistol-shot femoral pulsation (Traube sign)
• Rapid rise, rapid fall pulse (Water hammer sign)
❖ Acute AR: have small LV cavity → cannot ↑↑ SV → ↓↓ COP → acute pulmonary

edema (different from chronic AR)
❖ Aortic regurgitation murmur:

• ↑↑↑ SV → pounding / uncomfortable feeling when he lies of left side
• Early blowing early diastolic decrescendo murmur → best at left sternal
border
❖ Bicuspid aortic valve (QID: 2106)→ asymptomatic patient, with soft systolic
ejection crescendo-decrescendo murmur best heard at A1 (right sternal
border), with ejection click
❖ Mitral stenosis:
o Opening snap (OS): heard shortly after S2 … during opening of the mitral
valve.
o After mitral valve opening (during rapid filling of the LV) there is abrupt
halt of the MV opening due to fusion → result in opening snap.
❖ Mitral stenosis & RF
o > 99% of MS are due to RF with 10 – 20 years latency period (MS appear at
4th – 5th decade)
o In isolated MS: diastolic LV pressure is normal or decreased.
o ↑↑ LV pressure suggest combined aortic disease (co-exist in 25%) mostly AS & AR
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❖ The most reliable indicator of severity of MS is duration between S2 (A2
component) & opening snap, mean tans-valvular pressure gradient
❖ Describe Ortner syndrome: left atrial enlargement cause compression of the

recurrent laryngeal nerve (neuropraxia) causing paralysis of laryngeal
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muscles.
OS is due to forceful opening of the mitral valve during diastole, due to LA
pressure
Mitral Valve Prolapse (MVP)

most patients asymptomatic, if symptoms, presents with palpitations, chest pain (not
associated with CAD or MI), exertional dyspnea, fatigue, cough, orthopnea, rarely
presents as a panic disorder
auscultation findings:
1.) Mid-Systolic Click: due to sudden tensing of chordae tendineae, decreased
preload moves click closer to S1, best heard over apex, loudest just before S2,
usually benign
2.) Late Systolic Crescendo Murmur: if regurgitation present
❖ MVP is the commonest cause of subacute infective endocarditis in developed

countries especially when co-exist with regurgitation. (other causes are
valve sclerosis, prosthestic valves)
❖ Causes of morbidity & mortality in Marfan syndrome:

1) Cystic medial degeneration of the aorta → aneurysma dilatation →
dissection
2) Mitral valve prolapse → MR → cardiac failure
Mitral Regurgitation
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causes:
1.) Chronic RF/Infective Endocarditis,
2.) Chordae Tendineae Rupture,
3.) Mitral Valve Prolapse,
4.) Ischemic Heart Disease: post MI,
presents with dyspnea, orthopnea, fatigue, symptoms occur if regurgitation develops
acutely or if atria can no longer compensate in chronic disease
❖ Describe the pathogenesis of acute MR

• Preload ↑↑ massively as the LA have same length, no time for ↑↑ size and
compliance → pulmonary edema
• ↑↑ preload → ↑↑ LVEDV, due to ↓↓ resistance to the outflow of the LV
across the mitral valve → ↓↓ afterload ➔ ↑↑ EF , but most of the EF go to the
LA
❖ Describe the pathogenesis of chronic MR
• Due to eccentric hypertrophy of the LV → it can maintain the forward stoke
volume even with ↑↑ regurgitation flow
❖ Chronic mitral regurgitation:
o The best indicator of severe MR is audible S3 heart sound→ left sided
volume overload.
o The absence of S3 exclude severe chronic MR
o In hemodynamic maneuvers. Squatting = passive leg raising, Valsalva =
abrupt standing
o S4 may be normal in healthy older adults.
❖ Functional mitral regurgitation :

o S3 Gallop → ↑ LV illing rate during mid-diastole
o Commonest cause of MR → MVP
o ↓↓↓ afterload (by diuretics) → ↓↓ intraventricular systolic pressure →
↓↓ SV→ ↓↓↓ MR murmur with any cause
o ↓↓ preload totally eliminate the functional cause
o Mitral annulus calcification → rarely cause any murmur, have no
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significant hemodynamics
Tricuspid Regurgitation –
systolic murmur, retrograde blood flow into RA that occurs throughout systole,
similar to Mitral Regurgitation/Insufficiency, but softer due to lower pressure in
pulmonic circuit,
causes:
1.) Carcinoid Heart Disease: symptoms begin when GI tumor metastasizes to liver
(any hormones produced distal to liver in venous system metabolized by MAO in
lungs), produces 5-HT which fibroses tricuspid and pulmonary valves,
2.) IV Drug Use: results in right heart endocarditis (S. aureus), presents with pulsatile
liver due to increased venous pressures behind the right heart
❖ Describe carcinoid heart disease:
• ↑↑ serotonin → stimulate fibroblast, finrinogenesis ➔ plaque like
endocardial deposits of fibrous tissue → tricuspid regurgitation &
pulmonary valvopathy → RSHF
• Normal
Notice the difference between the SBP & DBP in the aorta
• Aortic regurge
- Loss of diacrotic notch
- Steep decline in aortic pressure → ↑↑ PP
Murmur will be heared immediately after closure of aortic valve (early
diastolic) just after closure of aortic valve
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• Mitral regurge
- Murmur heard at the opening of the aortic valve
Notice the markedly ↑↑ LA pressure → early & large V wave in the LA tracing
• Aortic stenosis
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• Mitral stenosis
286
o Phase 3a – Rapid Repolarization

Rectifier (voltage-gated slow) K+ channels OPEN, L-Type Ca2+ channels
DEACTIVATE, and ryanodine receptors CLOSE
o Phase 3b – Restoration of Ion Balance
SERCA Ca2+ pump ACTIVATES, pumps Ca2+ back into sarcoplasmic reticulum to
store until next Phase 2
NCX Na+/Ca2+ exchanger pump ACTIVATES, pumps 1 Ca2+ out of myocyte in
exchange for 3 Na+ in
o Phase 3c – Preparation for Subsequent Contraction
Voltage-gated Na+ channels OPEN (but are still INACTIVE), occurs when
repolarization returns membrane potential to about -50 mV
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o Phase 4 – Reestablishment of Na+/K+ Gradient
Voltage-gated Na+ channels ACTIVATE (but are now CLOSED) and Na+/K+ pump
restores Na+/K+ gradient
Na+ channels activate when repolarization returns membrane potential to about
-85 mV
❖ Mechanism of uptake of calcium from cardiac myocyte before relaxation:

• NCX (Na/ Ca exchange pump)√√: remove 1 intra-cellular Ca, in exchange
of 3 Na
• SERCA (SR calcium ATPase pump): Ca ATPase exchange pump actively
transfer cytosolic Ca to ER
287
Pacemaker action potential
o Phase 4 – Spontaneous Depolarization

Slow, spontaneous diastolic depolarization as “leaky” mixed Na+/K+ channels
slowly move membrane potential to threshold
This mixed Na+/K+ current is the “funny” or pacemaker current (If or IKf), different
from INa in Phase 0 of ventricular action potential, accounts for automaticity of
SA and AV nodes
There is also a slow decrease in K+ efflux which began during phase 3
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(repolarization) of the previous action potential
Once membrane potential reaches -50 mV, T-type (transient) Ca2+ channels open,
allowing Ca2+ to enter cell and contribute to depolarization
As action potential approaches -40 mV, L-type (long-lasting) Ca2+ channels will
open, triggering an action potential (see Phase 0 below)
Slope of Phase 4 in SA node determines HR:
• ACh/Adenosine decrease rate of spontaneous diastolic depolarization, thus
decreasing HR,
• Adenosine interacts with A1 receptors on surface of cardiac cells, results:
1.) K+ Channel Activation: increases K+ conductance, causing membrane
potential to remain negative longer,
2.) L-Type Ca2+ Channel Inhibition: further prolongs depolarization time,
both actions result in slowing of sinus rate and increase in AV nodal conduction
delay, thus Adenosine used to terminate paroxysmal supraventricular
tachycardia, ACh acts similarly (also increases outward K+ conductance while
decreasing inward Ca2+ and Na+ currents during Phase 4)
o Phase 0 – Rapid depolarization

L-Type voltage-gated Ca2+ Channels OPEN leading to upstroke and membrane
potential rapidly climbs from -65 mV to +52 mV
Fast voltage-gated Na+ channels permanently inactivated
o Phases 1 and 2 absent

o Phase 3a – Repolarization
Rectifier K+ channels OPEN leading to K+ influx, L-Type Ca2+ channels DEACTIVATE
o Phase 3b – Restoration of Ion Balance
NCX Na+/Ca2+ exchanger pump ACTIVATES, pumps 1 Ca2+ out of myocyte in
exchange for 3 Na+ in
o Phase 3c – Preparation for Subsequent Contraction
L-Type Ca2+ Channels ACTIVATE (but are now CLOSED)
Na+/K+ Pump Restores Na+/K+ Gradient
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❖ Arrhythmia Physiology – mechanism of arrhythmias:
DISORDERS OF IMPULSE FORMATION:
1.) Increased Automaticity: largely due to genetic alterations of membrane
channels,
2.) Triggered Afterdepolarizations: either early (EADs) or delayed (DADs),
- Early Afterdepolarization (EAD): triggered by spontaneous SR Ca2+ release or
delayed Phase 3 repolarization (because membrane stays closer to threshold
longer), caused by acute MI, β adrenergic activity, or Digitalis/Digoxin
toxicity, typically may lead to VTAC and Torsades de Pointes,
- Delayed Afterdepolarization (DAD): triggered by long QT syndrome drugs, more
likely to occur with bradycardic conditions,
DISORDERS OF IMPULSE CONDUCTION: some sort of
3.) Block or 4.) Reentry Pathway: area where split occurs in a conduction pathway
with a fast and slow half of the loop, slow half conducts signal slowly enough that
by the time the signal rejoins the fast half at the end of the split, the fast half is
no longer refractory, causing slow loop to reactivate it – this happens over and
over, caused by genetic influences (either acting alone or with some
environmental insult), ischemia, acidosis, high sympathetic activity, drug
(Digitalis/Digoxin) toxicity, electrolyte imbalance (esp. K+ and Ca2+), myocyte
damage due to MI,
TYPES OF ANTIARRHYTHMICS:
1.) RATE control Drugs (Class 2 and 4 Antiarrhythmics): slows HR in tachycardic
patients, usually patients who are severely bradycardic do not take drugs, they
get a pacemaker,
2.) RHYTHM control Drugs (Class 1 and 3 Antiarrhythmics): regulates rhythm to
make it more even rather than trying to slow it down or speed it up (though they
may do either in the process of regulating it), acts by prolonging QT interval (time
between atrial and ventricular depolarization)
29
288
289
❖ Wolff-Parkinson-White (WPW) Syndrome

❖ Wolf Parkinson white syndrome :
o Commonest re-entrant SVT (paroxysmal, narrow QRS)
o Normally show widened QRS;;;; in re-entrant tachycardia → QRS
become narrow as the bundle of Kent no longer pre-excite the
ventricles but form re-entrant circuit back to atrium.
30
290
❖ Atrial fibrillation :
o ECG : low amplitude fibrillary waves may exist
o Most common site of focus is pulmonary veins
o Atrial HR → due to ↓↓ ERF & incinc conductivity of the atria
o Ventricular response → dependant on the ERF of the AV Node,
most of the atrial pulstions never reach the ventricles.
o Ventricular myocyte ERF is not an obstacle as it may reach HR up to
300 beat / min.
❖ Atrial fibrillation :
 Pulmonary veins → are the commonest origin of AF
 Left atrial appendage (LAA) → is the commonest site of thrombosis in AF
patients
• LAA is sac like structure in the LA, contribute to 90% of thrombosis of LAA
associated with non-valvular AF → can lead to embolism
❖ Biventricular Pacemaker – fed through subclavian vein into SVC, then into RA,
then RV (if only 2 leads), if 3 leads, 3rd is fed through coronary sinus, then
advanced into lateral venous tributary to pace LV
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❖ Lightning Injury
❖ What is the “holiday heart syndrome”:

Development of new onset atrial fibrillation after consumption of excess amount
of alcohol
❖ Paroxysmal SVT:
• Most commonly due to re-enterant impulses at AV node
• Acute termination by vagal maneuvers e.g. carotid sinus massage,
Valsalva maneuver, cold water immersion.
• Massage → ↑↑ firing of the carotid sinus → ↑↑ parasympathetic tone →
slow conduction through AV node & ↑↑ RF
❖ Complete heart block → atrium is contracted by SA node, while ventricles

contracted by AV nodes (slow pulse, still show normal QRS configuration),
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while below the AV node → very slow pulse (~ 20) with abnormal QRS
❖ Ventricular fibrillation is the most frequent mechanism of SCD in the 1 st 48 hr.
after AMI due electrical instability from the ischemic myocardium
291
❖ ANP & BNP also ↓↓ renin secretion
❖ Additional mechanism of action of BNP : (+) protect against the

myocardial remodeling and firoosis that occur in heart failure
❖ Mechanism of action of Neprilysin & clinical significance:
metalloprotease that inactivate peptides as BNP &ANP, glucagon, oxytocin,
inhibitors of neprilysin may be used to treat Heart failure.
❖ Some additional actions of ANP:
1) ↓↓ aldosterone secretion → ↑↑ Na & H2O excretion
2) vasodilatation of arterioles & venules, ↑↑ capillary permeability → ↓↓ blood
volume
292
❖ Reading of Swan Ganz catheter & how to locate the site of the catheter:
• The catheter is introduced through subclavian / IJV.
• Once reached SVC → venous pattern appear with small amplitude
oscillation
33
• When introduced to the RA → unchanged as SVC
• Introduced to RV → sudden rise of the systolic pressure with pulsatile
waveform, diastolic pressure is just below the RA pressure.
• Once it pass the pulmonary valve → sudden rise of the diastolic pressure
with no change in the systolic pressure (due to capillary resistance,
backward transmission of the LA)
• When the catheter tip is lodged inside the vein → venous type waveform
appear
❖ Pulmonary capillary wedge pressure
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CVS PATHOLOGY
294, 295
❖ Commonest cardiac anomaly associated with Down syndrome :

• The commonest type of endocardial cushion defect is complete AV
canal;
• Ostium primum ASD, VSD, single AV valve (between atrium & ventricle) →
AV regurge, Heart failure
❖ Digeorge syndrome ssociated with interrupted aortic arch (complete atresia)
❖ Coaractation of the aorta:
- Occur in 10% of patients with turner syndrome
- Clinical picture depend on the age of presentation
o Infant (PDA) → differential cyanosis
o Adult (closed PDA) → severe Heart failure, discrepancy of BP
❖ TGA: aorta become anterior & pulmonary artery become posterior
❖ Complete Atrioventricular Canal Defect
❖ Clinical picture of late PDA:

1) Pulmonary hypertension, due to left – right shunt
2) As the pulmonary pressure ↑↑ → the murmur diminished and eventually
disappear
36
3) Reversal of shunt & late cyanosis (Eisenmenger syndrome )
4) Differential cyanosis , as blood distal to left subclavian artery is
unoxiginated from PDA
❖ Patent Ductus Arteriosus (PDA) –

PDA normal in utero, where shunt is right-to-left and maintained by PGE synthesis
(from placenta) and low O2 tension)
Risk factors include prematurity and Rubella infection during 1st trimester
Treatments:
1.) Non-Surgical: Indomethacin (1st line, administered close to PDA),
contraindicated in Transposition of the Great Vessels (PDA necessary for
survival, Prostaglandin E used to keep PDA open),
2.) Surgical: required if Indomethacin fails in a child >6-8 months old
❖ Coarctation of the Aorta – aortic narrowing, types:

37
1.) Preductal: occurs proximal to ductus arteriosus,
2.) Juxtaductal: occurs near insertion of ductus arteriosus,
3.) Postductal: occurs distal to insertion of ductus arteriosus,
❖ Eisenmenger syndrome is due to pulmonary arterial hypertension → ↑↑

medial hypertrophy & ↑↑ pulmonary vascular resistance
❖ Normal oxygenation pattern in the heart

• Small VSD → L – R shunt with normal O2 in the LV, only O2 in RV ↑↑
• Large VSD → allow more mixing of blood → equalization of O2 in both – ↓↓
O2 in LV
❖ VSD murmur is usually cannot be heared at birth, audible around

4 – 10 days after birth as PVR ↓↓ → L to R shunt(N.B. large VSD
may not associated with murmur)
❖ Fallout tetralogy murmur which is heared at the sternal border is

due to pulmonary stenosis / supra-ventricular narrowing of the
38
pulmonary artery.
❖ Causes of cyanotic spells in TOF: dehydration, hyperventilation and mostly

idiopathic
296
❖ Cardiovascular Associations of Congenital Disorders
❖ Causes & importance of Isolated systolic hypertension:

• Causes: aortic sclerosis due to aging, severe AR, anemia, ↑↑ T3
• It I responsible for > 70% of hypertension in patients> 60 years (DBP is
normal), but ↑↑ SBP > 140 carry risk for CAD
❖ Why hypertension is a risk factor for aortic dissection:
- Longstanding hypertension → medial hypertrophy of the vasa vasorum →
↓↓ blood to the aorta → muscle weakness → dilatation of the aorta → more
tension on the aorta
39
❖ fibromuscular dysplasia (FMD)
o FMD typically occurs in women age <55.
o Characteristic pathology findings of fibromuscular webs alternating with
aneurysmal dilation and loss of the internal elastic lamina, is consistent
with fibromuscular dysplasia (FMD).
o Angiography (ie, percutaneous, CT, MRI) is diagnostic and typically
demonstrates a string-of-beads appearance in multifocal disease.
o FMD can involve any artery but most commonly the renal, cerebral (eg,
carotid, ertebral), and visceral arteries.
o Up to 80% of patients develop renal artery stenosis, which limits renal
perfusion and leads to activation of the renin-angiotensin-aldosterone
system.
o Other presentations are related to locations of the dysplastic artery;
cerebrovascular involvement (ie, headache, stroke, aneurysm rupture),
mesenteric ischemia, or extremity claudication may be seen … This young
woman with recent-onset hypertension died of an intracranial
hemorrhage, likely from a ruptured aneurysm.
❖ Blood pressure changes in patient with Obstructive Sleep Apnea:

• Systemic hypertension is due to chronic stimulation of the sympathetic →
↑↑ epinephrine
• Lose the normal diurnal variations in BP
❖ Hypertension→ the most important single risk factor to develop intimal tear
& formation of aortic dissection
Atherosclerosis → the most important cause of aortic aneurysms (esp.
abd)
❖ Definition of orthostatic Hypotension:
Orthostatic hypotension is defined as a reduction of 20 mmhg in systolic and
10 in diastolic.
297
❖ Types of xanthomas:
1) Eruptive xanthoma → yellow papules appears when TGs or cholesterol ↑↑
2) Tuberous & tendinous → Achilles tendon & extensor finger tendons
40
3) Plane xanthomas → liner lesions in skin folds associated with primary
biliary cirrhosis
4) Xanthelasma → peri-orbital palques, 50% with normal cholesterol level
❖ L/M of hyaline arteriolosclerosis:

- Chronic/repetitive endothelial injury caused by hemodynamic stress (in HTN) or
hyperglycemia causes leakage of plasma constituents across the vascular
endothelium and stimulates smooth muscle cell (SMC) proliferation and excessive
extracellular matrix production.
- It appear as homogenous deposition of eosinophilic hyaline glassy material in the
intima, media of small arteries and arterioles
- In DM it is concomitant with duration of disease and concomitant hypertension
❖ DD; Malignant hypertension (extreme or rapidly developing hypertension) causes

fibrinoid necrosis + hyperplastic arteriolosclerosis >>>>>>>> two things also.
• Fibrinoid necrosis is characterized by localized destruction of the vascular
wall with a circumferential ring of pink, amorphous material surrounding the
lumen.
• Hyperplastic arteriolosclerosis consists of onion-like, concentric thickening of
the walls of arterioles due to laminated layers of SMCs with intervening
basement membrane reduplication (onion skinning) … not seen if the cause
is uncontrolled diabetes.
298
Arteriosclerosis – hardening of arteries, with arterial wall thickening and loss of
elasticity
Arteriolosclerosis – common, affects small arteries and arterioles
Atherosclerosis (Peripheral Artery Disease) – very common, disease of elastic arteries
and large- and medium-sized muscular arteries
❖ Mention the steps of development of atherosclerosis:
1) Endothelial inury → endothelial cell dysfunction
2) Monocyte & lymphocyte migration into the intima → GFs
3) Platelets adhesion with the exposed collagen
4) GFs – smooth muscle cells migration (fibrous cap)
41
5) LDL cholesterol deposition in the intima
❖ Fibrous cap in atheromatous plaque is formed by vascular smooth muscle cells

(VSMCs). Endothelial cell injury → ↑↑ expression of vascular cell adhesion
molecule (VCAM) → ↑↑ adhesion & migration of T-lymphcytes & monocytes
→ ↑↑ GF & cytokines → proliferation of VSMCs
❖ Order of arteries affected in atherosclerosis :

• Abdominal aorta (especially at ostium) > coronaries > popliteal > carotid >
intra-cranial
• UL vessels are usually spared, mesenteric & renal arteries are usually
spared except at their ostia
❖ Second hold smoker (SHS) :

o Pre & post natal is the commonest cause (> 50%) of SIDS ➔ death of
well being child during sleeping
o Even parents smoke outside house must be encouraged to stop
smoking as the cigarette particles is transferred to child by skin,
clothes, hair
❖ Atherosclerosis
42
43
❖ Describe the cystic medial
degeneration, its clinical importance.
• It is characterized by myxomatous
degeneration of the media with
pooling of proteoglycans in the
medial layer
• It is characterized by
fragmentation of elastic tissue
(baset weave pattern)
• These fragmentations make cleft like
spaces in the media filled with ECM
matrix.
• It is caused by marfan syndrome , as it affect firillin-1 which is major ECM

component.
• These changes can be made by β amino-proprio-nitrile which inhibit lysyl
oxidase → ↓↓ cross linking elasti & collagen fibers.
❖ Pathogenesis of abdominal aortic aneurysm : all risk factors → ↑↑

oxidative stress, vascular smooth muscle apoptosis, chronic transmural
inflammation of the aorta → inflammatory cells → ↑↑ Matrix metalloprotease
& elastase → ↓↓ elastin & collagen → weakness of the wall & expansion
❖ Traumatic aortic rupture occur in the aortic isthmus as it is tethered by

ligamentum arteriosum → fixed unlike the whole aorta
299
❖ Dissecting aortic aneurysm :
• Stanford A : flap begin at the sino-tubular junction
• Stanford B : flap begin close to left subclavian artery
44
45
❖ Acute cornonary syndrome pathophysiology:
• Atherosclerotic plaques are usually asymptomatic except > 70% luminal
stenosis
• ACS occur due to plaque rupture → the likelihood of plaque rupture
is related to plaque stability rather than plaque size or degree
of luminal stenosis
• Plaque instability → depend on the mechanical strength of the fibrous cap
(thin cap are unstable, more risk of rupture)
• Thin cap fibroatheromas → large necrotic core covered by thin fibrous
cap, due to ↑↑↑ activity of macrophage metalloproteinases
• While ↑↑ stability usually occur by lysyl oxidase
❖ Coronary steal phenomena :

• Drugs responsible : Adenosine, dipyridamole → selective VD of the
coronary arteries.
46
• Usually used in myocardial perfusion imaging → generalized coronary VD
caused to exercise ➔ more hypo-perfusion & exacerbate ischemia
❖ Vasospastic angina :
o Occur at rest, night time.
o Triggered by: + amphetamines
o Ergotamines act as vasoconstriction due to its action on α receptors (partial
agonist) and serotonin receptors
300
❖ What is the factor that determine whether the plaque cause necrosis or not.
The rate of arterial occlusion, if the plaque developed slowly over time, it give
the coronaries the time to develop collaterals around point of occlusion. While
in rapidly developing plaque, no time for collateral circulation.
❖ Biochemical changes & effect of ischemia in myocardium in 1 min:

- The first changes of myocardial ischemia is cessation of aerobic
glycolysis & initiation of anaerobic glycolysis → ↓↓ ATP
- The depletion of ATP occur quickly in the most demanding area (the site of
contraction & Na/K pump) → occur in 60 seconds → loss of
contraction
❖ Biochemical changes & effect of ischemia in myocardium in < 30 min.:
- Restoration of blood < 30 minutes → myocardial stunning as full
power of contractility is not reversed immediately but take hours – days to
restore
❖ Biochemical changes & effect of ischemia in myocardium in > 30 min. :
- Persistant ischemia → degradation of ATP → AMP → adenosine ; which
is released in the blood to cause vasodilatation
- After 30 minutes → > 50% of adenine stores is depleted with irreversible
damage
❖ Describe the L/M changes of cardiac cells after MI in 0 -4 hr, 4 – 12, 12 – 24,
1- 5 days, 5 – 10 days, 10 – 14, 2 weeks – 2 months
47
❖ Describe process of myocardial hibernation: reduction of the
myocardial metabolism an function in case of myocardial ischemia to match
the new low level of O2, to prevent myocardial necrosis. It include ↓↓
responsiveness to Ca, sympathetic control ➔ ↓↓ contractility & LVEF, t is
reversible by reperfusion.
❖ Describe process of ischemic preconditioning: brief repetitive

episodes of myocardial ischemia & perfusion → protect the myocardium from
prolonged ischemia → myocardial death i.e. repetitive episodes of angina
prior to myocardial infarction → delay cell death after complete occlusion
❖ Which type of lesion. Coagulative necrosis
48
❖ Collagen in different stages of myocardial infarction
o Type III collagen → seen after 7 days after MI but eventually replaced by
type I
o Type I collagen → most abundant in mature scar tissue
❖ Reperfusion injury: after regaining normal perfusion, the cells paradoxically

die with elevated of enzymes → irreversible cell damage.
o Causes:
1) Free radicles production
2) Irreversible mitochondrial damage “mitochondrial permeability
transition”
3) Inflammation as blood attract more neutrophils
4) Activiation of complement pathway
301
❖ Evolving ECG changes seen in transmural MI:
1) Hyperacute T wave (1st sign) → due to localized hyperkalemia
2) ST elevation → follow the T-changes within minutes to hours.
3) Deep Q wave → appear within days
302
❖ Pathogenesis & Clinical picture , incidence of fibrinous pericarditis post MI:
• Clinical picture : sharp, pleuritic chest pain, +/- ↑↑ with swallowing →
posterior pericardium, +/- radiate to the neck → inf. Pericardium, +/- low
grade fever → inflammatory
• Incidence : 10 – 20% of STEMI, in 2 – 4 days
• Pathogenesis: nflammation localized to the region of the pericardium
overlying the necrotic myocardial segment , usullay short lived & treated by
aspirin
❖ Pathogenesis, incidence of Dressler syndrome:
• Incidence: < 4% of patients, occur from 1 week to few months
• Pathogenesis: MI expose antigen → provoke autoimmune generalized
49
serositis (pleuritis, pericarditis), usually respond to aspirin / steroids
❖ Atheromatous plaques in coronary arteries don’t produce
symptoms unless there are 75% luminal stenosis.
❖ Previous MI lead to ↓↓ risk of free wall rupture due to presence of fibrotic
scar, multiple collaterals which ↓ burden of the infarciton
❖ What is the type & character of reperfusion arrhythmia: Benign and not
associated with ↑↑ mortality, the commonest of them is acclereated
idioventricular (AIVR) rhythm
❖ Rupture of Inter-Ventricular Septum is associated more with LAD thrombus
❖ Treatment of post-infarction pericarditis: it is usually treated by aspirin

(acetaminophen is effective antipyretic and analgesic btu not anti-
inflammatory)+ colchicine,
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❖ L/M of cardiac amyloidosis :
- Cardiac amyloidosis ca occur as a result of systemic amyloidosis (AL),
mutated transthyretin, senle (wild type)
- L/M chow fascicles of normal myocardium with amorphous acellular pink
material (congo red stain)
50
❖ Hypertrophic cardiomyopathy :
o Commonest cause of SCD in athletes < 35 (33% in autopsy)
o Mostly asymptomatic → +/- dyspnea, fatigue, chain pain
o Histologically :
▪ Myocyte hypertrophy
▪ Muscular disarray of the muscle fibers (pic. 1)
▪ Abnormally looking myocytes. (pic. 2)
❖ LVOT obstruction caused by HOCM is due to hypertrophy of IVS & systolic

anterior motion of the mitral valve toward the IVS creating the obstruction.
❖ Familial HOCM is caused by mutations in β myosin heavy chain &
myosin binding protein
❖ Doxorubicin induced DCM :

o Cause DCM according to its cumulative dose due to, both inhibited by
dexrazoxone
1) Binding to topoisomerase II form complex → DNA cleavage
complexes → DNA breaks
2) Formation of iron containing complexes → free radicles (Fenton’s
51
reaction)
❖ Mention durgs that can be used & avoided in HOCM:

- Vasodilators (e.g. nitroglycerin, ACE-I, DHP-CCB) → ↓↓ afterload
- Diuretics → ↓↓ preload
• negative inotropic agents (NDHP-CCB, BB, disopyramide) are allowed
❖ Hypertrophic cardiomyopathy (HCM) :

• Murmur intensity depend on the LV end diastolic volume
• ↑↑ LV-EDV → ↑↑ LV chamber dimensions → ↑↑ separation between
hypertrophied septum & mitral valve → ↓↓ murmur
❖ Histological picture of HCM : (+) hypertrophy of myocytes & muscle bundles

+ widened interstitial spaces → fibrosis
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304
53
❖ Renin produced by juxta-glomerular apparatus, ACE enzyme present in small
pulmonary arteries
❖ Heart failure cells (occur in LV failure) occurs due to alveolar hemorrhage →
macrophage digest blood → hemosiderin → hemosiderin / iron (any
where) detected by perussian blue stain (not exclusively in hemochromatosis)
❖ Cardiogenic shock → ↓↓ LV filling → ↓↓ PCWP due to LA atrium.
❖ Pheocromatocytoma may lead to orthostatic hypotension due to ↓↓ plasma
volume
❖ Pulmonary hypertension in LV heart failure → ↑↑ pulmonary venous

congestion → damage to endothelium → ↓ NO & ↑ endothelin ➔
vasoconstriction & remodeling later on (less severe than in PAH, partially
reversible)
❖ Right sided heart failure ➔ normally predispose for edema due to ↑↑ capillary
hydrostatic pressure, but ↑↑ hydrostatic pressure → ↑↑ interstitial pressure →
↑↑ lymphatic drainage (which partially compensate the process);
appearance of edema occur when net filtration is overwhelm the capacity of
the lymphatic to drain the fluid.
❖ Clinical signs of LV failure :
1) Orthopnea ➔ most specific sign of severe LV failure, occur due to acute
exacerbation of baseline acute pulmonary edema due to redistribution & ↑↑
VR
Orthopnea also can occur without LV failure in case of MS
2) Wheezing on exertion (cardiac asthma)→ as exercise ↑↑ VR
❖ Commonest cause of decompensated LV failure? Excessive eccentric
hypertrophy lead to maladaptation → ↑↑ wall strength & ↓↓ contractility
305
❖ Mention the immunological & vascular manifestations of infective
endocarditis
54
❖ Difference between Janeway lesions, Osler nodules:
• Janeway lesions: nontender macular, erythematous lesions on palm &
sole. Due to septic emboli → consists of microabscesses
• Osler nodules: tender, violaceous nodules typically located in the pulp of
fingers and toes. Due to immune complex deposition in the skin
❖ Early penicillin treatment of Group A Strept is important for prevention of

ARF
❖ TRH & VIP can both ↑↑ production of prolactin
❖ Commonest site of infective endocarditis: commonest site of turbulent flow

ehich is either atrial surface of mitral / TC valve, ventricular surface
of A / P valve
Endocarditis
Risk factors include history of right heart disease, valvular heart disease, IV drug use,
immunosuppression, prosthetic valve, ASD/VSD
Types:
1.) Acute Endocarditis:
- caused by S. aureus (high virulence),
- large vegetations occur on healthy or damaged valves, esp. from Mitral Valve
Prolapse (most common predisposing condition) or Rheumatic Heart Disease,
- associated with IV drug users,
- presents with fever and rapid degradation of heart tissue,
2.) Subacute Bacterial Endocarditis:
- slower onset with less severe symptoms,
- caused by Enterococcus (GI/GU surgery), S. viridans (oral/dental surgery, low
virulence), S. epidermidis (prosthetic valves), S. bovis (gallolyticus, Ulcerative
Colitis or Colorectal Cancer),
- smaller vegetations occur on diseased or congenitally abnormal valves,
3.) Marantic Endocarditis:
- neoplastic syndrome (GI tract),
- sterile vegetations occur on valves due to increased coagulability caused by
increased mucin production (same process underlying Trousseau’s sign of
malignancy – different from the low calcium Trousseau’s sign),
55
- may produce emboli to periphery,
4.) Libman-Sacks Endocarditis:
- caused by SLE (“SLE causes LSE”),
- usually asymptomatic, but may cause Mitral Insufficiency/Regurgitation,
5.) HACEK Organisms:
- Haemophilus, Aggregatibacter (formerly Actinobacillus), Cardiobacterium,
Eikenella, Kingella, all fastidious G⊖ organisms (e.g. Coxiella burnetii,
Bartonella),
- suspect if fever with a murmur, but negative blood cultures,
Duke Criteria:
1.) Blood Cultures: obtain 3 separated in time and location, multiple positive
cultures of the same organism strong evidence for endocarditis,
2.) Echocardiography: look for vegetations, not ruled out by negative echo,
3.) CXR: may reveal septic emboli in right sided endocarditis,
Treat with prolonged empiric antibiotic therapy (low-dose Penicillin or Vancomycin),
surgical valve replacement,
Complications include chordae tendineae rupture, emboli, glomerulonephritis,
suppurative pericarditis, intravascular infection that can spread to other organs
(watch for signs of neurologic, joint, and lung manifestations)
❖ Marantic endocarditis = non-bacterial thrombotic endocarditis (NBTE)

• Causes of non-bacterial thrombotic endocarditis: mostly advanced
malignancy, may be assoiated with APL, SLE, DIC
• Pathogenesis of non-bacterial thrombotic endocarditis: cytokines produced
→ endothelial injury → platelets aggregation with fibrin, ICs → white
thrombus ➔ more liable to emblization than EC.
• Meaning of verrucous endocarditis → NBTE can cause variable sized
thrombi from microscopic structure to large masses called (verrucous )
• Incidence & Mechanism of non-bacterial thrombotic endocarditis in
malignancy: associated with mucinous adenocarcinoma due to pro-
coagulant effect of circulating mucin.
306
Rheumatic Fever/Rheumatic Heart Disease (RHD)
56
- Rheumatic Fever (RF) is a systemic immune process that may or may not lead to RHD,
- presentations (JONES criteria):
1.) Migratory Polyarthritis: no permanent damage, occurs at both large and small
joints,
2.) Endocarditis: most commonly affects high pressure valves first (sterile
vegetations at closure line of valve, mitral > aortic >> tricuspid), produces mitral
regurgitation or prolapse (early), or stenosis (late),
3.) Myocarditis: contains Aschoff bodies, which are granulomas surrounded by
reactive histiocytes called Anitschkow cells (enlarged macrophages with ovoid,
wavy, rod-like nucleus), pathognomonic for RHD),
4.) Pericarditis: friction rub,
5.) Erythema Marginatum,
6.) Subcutaneous Nodules: extensor surfaces,
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7.) Sydenham’s Chorea: involuntary movements of all muscles, late finding,
- serum shows elevated ESR and CRP,
- ECG shows leukocytosis-increased PR interval,
- ASO positive,
- positive throat culture,
- treat with Penicillin,
- acute morbidity most likely caused by pancarditis (inflammation of endocardium,
myocardium, and epicardium)
❖ Acute rheumatic fever :
o Syndeham Chorea :
▪ Hyperkinetic extra-pyramidal movement
▪ Commonest cause of acquired chorea of childhood
▪ Caused by delayed onset autoimmune reaction against basal ganglia
❖ Most acute morbidities & death from ACUTE rheumatic fever is due to
pancarditis → MR, myocarditis → Heart failure
❖ Acute rheumatic fever:

• Due to antigenic mimicry between bacteria and human
- M-protein → Myosin (cardiac)
- N-acetyl β D-glucosamine → Lysoganglioside (Nerve surface protein)
• Syndeham chorea → patiet often have sudden change in his
voice pitch & volume
• The most serious manifestations is pan-carditis → clinical picture: non
specific fever, fatigue, anorexia, altered vital signs
• Endocardial involvement: result in valvular dysfunction → Acute
mitral regurgitation.
• Also cause ARF related myocarditis
❖ Pericarditis pain → severe middle or left chest pain that radiate to the neck &
trapezius ridge
❖ Acute pericarditis may cause fluid accumulation inside the pericardial cavity
→ cardiac tamponade
❖ Constrictive pericarditis show rapid Y descent that becomes deeper &
steeper during inspiration.
58
307
❖ Histology of different causes of myocarditis:
• Acute rheumatic fever related myocarditis :
 Interstitial fibrosis with central lymphocytes & macrophages +
scattered multi-nucleated giant cells ➔ Aschoff body (myocardial
granuloma)
 Pumped macrophages with abundant cytoplasm & central, slender

chromatin ribbons ➔ Antischkow / caterpillar cells
 Aschoff bodies then replaced by fibrous scar → chronic mitral stenosis /
regurge
• Hypersensitivity myocarditis : due to medication, interstitial infiltrate
with EOSINOPHILS
• Viral myocarditis: LYMPHOCYTIC interstitial infiltrate, with focal
necrosis of myocytes.
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❖ Pulsus paradoxus technique (QID: 2099):
• During BP measurement; 1st Korotkoff sound is heared when SBP just <
cuff pressure.
• During expiration BP > BP during inspiration
• If you heared the 1st Korotkoff sound only dueing expiration (so SBP in
inspiration is lower), the first BP when you hear Korotkoff sound in both
inspiration & expiration (this correspond to BP) difference between two if
> 10 = pulsus paradoxus due to impaired filling of the RV → bowing of the
IVS to the LV cause its diameter to ↓↓
• Normally there is difference in IPP during inspiration ~ 2-5 mmHg, in COPD &
BA this drop is greatly exaggerated (commonest cause of pulsus paradoxus in
absence of pericardial disease)
❖ Cardiac tamponade :
o During LV expansion at diastole → fluid displaced ➔ prevent RA expansion
→ late diastolic collapse of the right atrium.
o During diastole & inspiration → ↑↑↑ VR to the right atrium → RV ➔
expansion of the right ventricle ( cannot expand outward) so press on the IVS
cause bulge of the IVS to the LV → ↓↓ LV EDV → ↓↓ LV SV → SBP & pulse
60
(pulsus paradoxus)
o Electrical alternans → occur in very large pericardial effusion
o Other causes of pulsus paradoxus : COPD, hypovolemic shock,
constrictive pericarditis
❖ Acute rejection of cardiac transplant:

• Incidence & mechanism of Acute rejection of cardiac transplant:
- Occur in 40% of transplantation
- Mainly due to cell mediated immunity (host T-lymphocyte sensitization
against graft MHC antigens) , rarely due to anti-donor host antibodies
(diagnosed by direct immunofluorescence)
• Histological appearance of Acute rejection of cardiac transplant: appear by
symptoms of Heart failure in 1 – 4 weeks after transplantation,
endomyocardial biopsy show dense infiltrate of mononuclear cells of T-
lymphocytes
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308
❖ Clinical picture of GCA:

• Headache →
o Ofcal pain & tenderness over the temple
o Scalp temple with combing
o Nodularity, thickening on palpitation of the temporal area
• Optic neuropathy → reversible / irreversible vision loss
• Craniofacial pain syndrome
o Jaw, tongue claudication & facial pain
o Pain induced by mastication (due to inability to ↑↑ blood supply due
to narrowing of the arteries)
• Polymyalgia rheumatica (>50%)
❖ Giant cell arteritis (GCA):

• High suspicion of GCA → best initial management is acquisition of
CRP / ESR → high levels → give steroids & biopsy to confirm diagnosis
• Although it is due to cell mediated & humoral mediated immune reponse,
the cellular immunity is much more important
• Inflammatory infiltrate seen composed of lymphocytes, macrophages,
multi-nucleated giant cells.
• The production of IL-6 correlate with the severity of the disease ,
monoclonal antibodies against IL-6 (tocilizumab) is effective treatment.
• Antibodies to myeloperoxidase (MPO-ANCA) & proteinase 3 (AP3-ANCA)
❖ Describe the histological findings in GCA (identical to Takayasu)

• Scattered focal granulomatous inflammation centered on the media,
intimal thickening, elastic lamina fragmentation, giant cell formation
(without granuloma)
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Medium Vessel Vasculitides
- Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)
- Polyarteritis Nodosa
- Raynaud Phenomenon
- Thromboangiitis Obliterans (Buerger Disease)
❖ What is the important association of polyarteritis nodosa: 30% associated

with HBV
❖ Biopsy of PAN will see what changes? Segmental, transmural inflammation of
the arterial wall with fibrinoid necrosis (circumferential ring of pink material
surround the vascular lumen)
❖ Polyarteritis nodosa:
• Spares the pulmonary arteries, very rarely affect bronchial arteris
• 1/3 of patients have cutaneous manifestations e.g. livedo reticularis,
palpable purpura
❖ Berger disease :
• Acute & chronic inflammation of medium & small sized vessels (mainly tibial
& radial) with extension of the inflammation to the surrounding
veins & nerves
• Clinical picture : Rest pain →nerve, Raynaud’s phenomena → artery,
thrombophlebitis → veins
63
• More common in ́♂ < 35 years in Israel, Japan, India ≫ US & Europe
❖ Kawasaki Disease (Mucocutaneous Lymph Node Syndrome) –
❖ Clinical picture of Kawasaki disease :
Small Vessel Vasculitides with Immune Complexes

- Cryoglobulinemia – vasculitis affecting skin, GI, and renal systems, no joint
involvement (contrast Henoch-Schönlein Purpura which has joint involvement),
caused by antibodies that condense at decreased temperature, IgA deposits with
cryoglobulins, adults, associated with Hepatitis C, Type 1 Membranoproliferative
Glomerulonephritis, presents with Raynaud Phenomenon, palpable purpura
- Rickettsial (ANCA-Positive) Vasculitis – vasculitis affecting the skin, caused by
immune reaction to Rickettsia rickettsii, presents with Rocky Mountain Spotted
Fever (RMSF), petechiae on extremities that spreads to trunk
- Henoch-Schönlein Purpura
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Small Vessel Vasculitides without Immune Complexes
- Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
- Granulomatosis with Polyangiitis (Wegener’s Granulomatosis)
- Microscopic Polyangiitis
- Primary Pauci-Immune Crescentic Glomerulonephritis – vasculitis limited to
kidney, “paucity” of antibodies, histologically indistinguishable from renal
involvement of Microscopic Polyangiitis or Granulomatosis with Polyangiitis, p-
ANCA (MPO-ANCA) antibodies (neutrophil myeloperoxidase)
❖ Clinical & laboratory features of Churg Strauss polyangitis:
- Eosinophilic granulomatosis with polyangitis
- Clinical picture:
• Late onset asthma, transient pulmonary nodules
• rhinosinusitis, PNS abnormalities
• Mono-neuritis multiplex , skin nodules → due to vasculitis of the
epineural vessels → nerve damge
- Lab : eosinophilia, P-ANCA
❖ Cutaneous small vessel vasculitits:

• Affect skin only, palpable non-blanching cutaneous purpura affect mainly
lower limbs
• Caused by exposure to drugs, pathogens including penicillins
• L/M: markedly inflamed BV + fibrinoid necrosis → with neutrophils invade
perivascular space (leukocytoclastic vasculitis) older lesions →
mononuclear cells
❖ Lacunar infarction:
• Form of ischemic stroke involving the small penetrating arterioles → deep
brain matter
• Cardiac embolism & atherosclerosis → medium & large size artery
65
• Chronic hypertension → lipo-hyalinosis, micro-atheroma formation,
sclerosis of the vessel (hypertensive arteriolar sclerosis) →
progressive narrowing of the arteriolar lumen → thrombotic vessel
occlusion
• CT initially free due to small sized stroke.
• Clinical picture :
- Posterior limb of the IC → pure motor stroke, ataxia-hemiplegia
syndrome, very rarely cause pure sensory stroke
- Genu of the IC → Dysarthria – clumpsy hand syndrome
- VPL / VPM of the thalamus → pure sensory stroke
309
❖ Left atrial myxoma:
• Clinical picture : the mass produce large amount of IL-6 which cause the
constitutional symptoms, cause valve obstruction by the myxoma so
the cardiovascular symptoms are positional, the mass ma be very large in
size with emboli, myxomas produce very large amounts of growth
factors → angiogenesis which lead to hemorrhage
• L/M: scattered cells with mucopolysaccarides, abnormal BV, bleeding
66
CVS PHARMACOLOGY
310
❖ hypertension (+)
• BPH → α 1 blockers
• CHF / CAD → β blocker
• Essential → HCTZ
• DM → ACE-I
• Prinzmetal angina / Raynaud’s disease → Dihydropyridine CCB (2nd line)
❖ Treatment of acute decompensated heart failure: IV loop diuretic is

used as it is the most potent diuretic and cause symptom relief & diuresis in
the shortest time
❖ Drugs lower mortality in Heart failure → beta blocker (MBC), ACE-I, ARBs,
spironolactone
BB shouldn’t be used in decompensated state, wait till the patient stabilize and
slowly introduce the drug
❖ β blockers used to treat hypertension with co-morbid conditions as

migraine (as it ↓ AT-II thus ↓↓vasoconstriction) , essential tremors,
angina, previous MI, AF
❖ ACE-I & ARBs are not only important in Heart failure due to ↓↓
hypertension, but it has independent effect to ↓↓ cardiac
remodeling
❖ Difference between rise in creatine level due to ACE-I or ARF due to ACE-I
• Rise in serum creatinine up to 30% within 2 – 5 days after ACE-I is
67
common, stabilize after 2 – 3 weeks & reversible
• For patients dependent on efferent arterioles (e.g. RAS, AHF, CKD) →
ACE-I cause acute renal failure
❖ First dose hypotension in ACE-I :
• Hypotension is significant with ↑↑ renin as in ↓↓ volume (diuretics), Heart
failure
• Mechanism: use of ACE-I → significantly ↓↓ vasoconstriction effect of AT-II
• So begin ACE-I at low dose and gradual titration.

❖ Effects of ACE-I, ARB :
Drug Renin AT-I AT-II Aldosterone Bradykinins
ACE-I ↑↑ ↑↑ ↓↓ ↓↓ Increased
ARBs ↑↑ ↑↑ ↑↑ ↓↓ No change
311
Calcium Channel Blockers – Dihydropyridines

o Mechanism: acts on vascular smooth muscle, blocks voltage-dependent L-type
calcium channels of vascular smooth muscle decreasing muscle contractility,
efficacy: Amlodipine = Nifedipine > Diltiazem > Verapamil
o Treats: HTN, angina (including Prinzmetal), Raynaud Phenomenon (all except
Nimodipine), Subarachnoid Hemorrhage to prevent cerebral vasospasm
(Nimodipine), hypertensive urgency or emergency (Nicardipine, Clevidipine)
o Side Effects: peripheral edema, flushing, dizziness, gingival hyperplasia
o Amlodipine, Clevidipine, Nicardipine, Nifedipine, Nimodipine
Calcium Channel Blockers – Non-Dihydropyridines

o Mechanism: acts on heart, blocks voltage-dependent L-type calcium channels of
cardiac smooth muscle decreasing muscle contractility, efficacy: Verapamil >
68
Diltiazem > Amlodipine = Nifedipine (“Verapamil = ventricle”)
o Treats: HTN, Angina, AFIB/Atrial Flutter
o Side Effects: cardiac depression, AV block, hyperprolactinemia, constipation
o Diltiazem, Verapamil
69
312
70
❖ Deverse effects of nitrites: headache, flushing hypotension, lightheadedness,
reflex tachycardia,
❖ Around the clock administration of nitrates will lead to rapid tolerance to the
drug, so nitrate free period must be provided every day, this period is
preferred to be at night (the patient is sleeping & least cardiac load)
❖ Nitroglycerin :
o Low doses → dilate veins, higher doses → + arterioles.
o Know the composition
❖ Additional actions of nitrate:
- mild ↓↓ in afterload die to systemic vasodilatation
- mild coronary vasodilatation
71
❖ Mention the mechanism of action of milrinone, inamrinone
• Used in some cases of refractory Heart failure as inotropic agents
• PDE-3 inhibition → ↑↑↑ cAMP in (same as cilostasol, dipyridamole):
 Cardiac cells →↑ Ca influx → ↑↑ contractility
 Smooth muscle → systemic arterial & venous dilatation → ↓↓ BP
313
❖ Lipid lowering drugs :

• Fibrates : act by ↑↑ PPARα → ↓↓ VLDL production, ↑↑ LPL
• ω3 fatty acid → ↓↓ VLDL production, ↓↓ synthesis of apoB lipoprotein.
• Pro-protein convertase subtilisin kexin 9 (PCSK9) inhibitors →
monoclonal antibodies → ↓↓ LDL receptor degradation in the liver → ↓↓
cholesterol
• ↓↓ HDL → ↑↑ risk of CVS diseases
72
• Non pharmacological treatment for ↑↑ HDL → highest benefit for HDL &
CVS diseases
• Uses of medications to ↑↑ HDL levels don’t improve cardiovascular
outcome
• Statins → ↓↓ LDL
• Fibrates → ↓↓ triglycerides (30%)
• Niacin → ↑↑ HDL
• Ezetimibe → +/- ↓ LDL
• Weight loss & exercise → ↓↓ triglycerides
❖ Fibrates & lipid lowering drugs:

• Fibrates act by ↑↑ PPAR-α → ↑↑ synthesis of LPL → destruction of
triglycerides
• Fibrates → ↓↓↓ TGs, Statins → ↓↓↓ LDL, niacin → ↑↑↑
HDL
❖ Statins → ↓ de novo cholesterol synthesis → ↑ LDL receptor density
• Other functions of statins that is important :
1- Anti-inflammatory properties
2- Improve endothelial dysfunction
3- Stabilize atherosclerotic plaques
❖ Describe the metabolism & pharmacokinetic of statins :

• Statins (except parvastatin) are metabolized by CYT P450 3A4 → so
concurrent use of any inhibitors of CYT P450 will ↑↑ toxicity →
rhabdomyolysis ….
❖ Statin therapy, obtain base line liver function tests before starting the therapy,
otherwise no routine monitoring is needed except symptoms appear.
❖ Statin induced myopathy usually mild muscular pain, may cause ↑↑ CK &
rhabdomyolysis with concurrent use of fibrates (↓↓ clearance of statins), also
myopathy risk ↑↑ by use of niacin & ezetimibe (but to lesser extent)
myopathy is the most common adverse effect in statins
73
❖ Lipid lowering drugs :
➢ Statins : ↓↓ hepatic cholesterol synthesis → ↑↑ LDL receptors on liver to ↑↑
uptake of LDL from blood
➢ Bile acid resin → ↑↑ bile salt synthesis → ↑↑ uptake of LDL from blood to ↑↑
hepatic cholesterol synthesis
➢ ↓↓ hepatic cholesterol synthesis → ↑inc HMG-CoA reductase ➔ Adding
statin to drugs further reduce LDL (synergistic effect)
o Fibrates :
▪ Actions
1) ↑↑ LPL
2) ↓↓ cholesterol 7 α hydroxylase → ↓↓ bile salt formation & ↑↑ cholesterol
excretion → ↑↑ precipitation of crytals → ↑inc GB stones
3) ↑↑ PPAR-γ
o Fish oil ➔ ↑↑ ω3 fatty acids → ↑↑ bile acid synthesis → ↓↓ cholesterol
saturation in bile → ↓↓ Gall stone formation
❖ side effects of bile acid resin:
• GI upset (diarrhea)
• ↓↓ absorption of nutrients & drugs
• ↑↑ hepatic production of triglycerides (# fibrates)
• ↑↑ VLDL in circulation
• These changes are side effects not related to mechanism of action of the
drug
74
Fish Oil/Omega-3 Fatty Acids
o Mechanism: decreases VLDL and apolipoprotein B synthesis
o Treats: Triglycerides, HDL
o Side Effects: fishy taste
314
75
❖ Digoxin toxicity :
• Although hypokalemia can precipitate digoxin toxicity, digoxin toxicity
cause ↑↑ potassium level.
• The most serious complication is cardiac arrhythmias (any type)
• AF – RVR → 1st line: BB, CCB. 2nd line: Digoxin (especially if there is
Heart failure)
❖ Digoxin as anti-arrhythmic drug:
o Used in Af/ AF RVR, although CCB, BB are better
o Due to para-sympatho-mimetic action ➔ a) enhance efferent vagal
ganglionic transmission b) sensitize arterial baro-receptors augment
afferent input
❖ Digoxin is renal cleared (no role of liver in Digoxin) → elderly have

progressive loss of renal functions without concomitant rise in serum
creatine, so any renally excreted drugs should be reduced in elderly even
with normal renal functions
❖ Action of digoxin:
76
315
❖ Effect of anti-arrhythmic drugs on AP duration:

• Class IA: has moderate effect on K channels → prolongation of the
repolarization → ↑↑ duration of AP
• Class IB: can block the ‘plateau’ Na current → ↓↓ duration of AP
• Class IC: although , it is the strongest one in use dependeance (block
phase 0), it done affect the duration of the AP
77
❖ Mention the effect of antiarrhythmic drugs on QRS & QT duration
• Class IA → ↑↑ QRS duration (due to Na block), ↑↑ QT interval (moderate K
block)
• Class IB → no effect on QRS, QT (due to rapid dissociation)
• Class IC → ↑↑ QRS duration (strong blockage on Na), normal QT interval
• Class III → no effect on QRS, ↑↑ QT interval , ↑↑ AP duration
❖ Mention the effect of class IC on the AP duration?
• The drugs act mainly on the fast conducting pathways as it cause use
dependenace
• It cause ↑↑ QRS duration without changing the total AP duration
or QT interval
• So class 1C lengthen the duration of QRS in rate dependant manner
(normally in exercise, ↑↑ HR but the QRS duration slightly reduced)
❖ Why class IB is used mainly in post infarction arrhythmia:
- Class IB bind avidly to the inactivated Na channels, because normal cells
has short refractory period so they are dissociated so rapidly (no effect on
QRS in normal heart)
- Ischemic myocardium → less negative RMP → more to be depolarized →
inactivated fro longer period → more bind specifically- to the ischemic
tissues
78
❖ Use dependence of anti-arrhythmic drugs :
• Anti-arrhythmic drugs bind to activated & inactivated Na channels,
79
dissociate in resting state (state dependence).
• So tissues that more frequently depolarized (tachycardia) → more to be in
activated & inactivated state → more binding to drugs → more blockage
(use dependence)
• Class IB: have the weakest binding of class I drugs → dissociation of drugs
is so rapid ➔ little use dependence
 More selective for ischemic myocardium → less negative RMP → take
more time in repolarization (more time to be in inactivated state) →
more drug binding → ischemia induced VTac
• Class IC: have the stongest binding → highest use dependenace → use to
terminate tachyarrhytmias
 Class IC usage → excessive delay in conduction speed that promote
arrhythmia (especially in ischemic patients)
• Affection of Phase 0 depend on the use dependence → class IC > A > B in
case of phase 0 inhibition
316
80
❖ Amiodarone is class III anti-arrhythmic rug cause prolongation
of QT interval → but very little risk of torsade des pointes (due to its
homogenous effect on ventricular repolarization)
❖ What are the thyroid complications of amiodarone.

• Thyroid complication is more common with preexisiting thyroid disease
so TSH sould be assessed to diagnose any subclinical affection
• Hypothyroidism: ↓↓ production of thyroid hormones
• Hyperthyroidism: ↑↑ synthesis or destructive thyroiditis with preformed
thyroid hormone.
❖ Other side effects associated with amiodarone. (+) peripheral neuropathy,
optic neuropathy, hepatitis & ↑↑ AST & ALT
❖ Class III antiarrhythmic drugs → block K channels → ↑↑ duration of AP

❖ Class III anti-arrhythmic drugs used to maintain sinus rhythm in patient with
paroxysmal AF. ………………………… class III against L-type Ca channels
❖ Sotalol is an class III anti-arrhythmic drug + class II properties.
317
81
❖ Class IV anti-arrhythmic drugs (e.g. verapamil) → prevent recurrent nodal
arrhythmias (paroxysmal SVT) → block L-Ca channels in SA nodes (slowing
phase 0), block T-Ca channels (slowing phase IV)
❖ Adenosine → open K channels → ↑↑ outward current → more negative AP →

briefly block the conduction in the AV node. Adenosine also is coronary
vasodilator
❖ Constipation is a major side effect of CCB → verapamil > Diltiazem
❖ Other drugs cause QT prolongation: (+) class IA, III anti-arrhythmics

(Quinidine, sotalol), methadone
82
83

UW Notes - 7 - Cardiology Arranged

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CVS EMBRYOLOGY

❖ Outflow Tract Formation

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Fashion Backpack for Stylish Stethoscope Cover

❖ How you can diagnose paradoxical (cryptogenic) stroke:

❖ Borders of the heart in CXR:

❖ Cardiac Anatomy in Normal Aging

❖ Complication of cannulation of CFA above the inguinal ligament: injury to the

❖ Inferior surface of the heart :

❖ Mention the blood supply of the papillary muscles:

❖ To access the left side of the heart, there are 2 approaches:

❖ Subclavian steal syndrome:

❖ Cardiac & vascular function curves in Arteriovenous Fistula –

• Acute AV fistula: ↑↑ COP & ↓↓ TPR, but no ↑↑ of MAP initially. By time

❖ Effect of nitroperruside on flow-loop curve:

❖ Describe the normal finding of aging process in the heart:

❖ Oscaltatory findings in AS (other than murmur) : ↓↓ S2, ↑↑ S4

❖ Holosystolic murmurs are TR, MR, VSD;

❖ Pathological changes that lead to formation of MVP: proliferation of spongiosa

❖ Clinical findings of chronic aortic regurge:

❖ Acute AR: have small LV cavity → cannot ↑↑ SV → ↓↓ COP → acute pulmonary

❖ Aortic regurgitation murmur:

❖ Describe Ortner syndrome: left atrial enlargement cause compression of the

Mitral Valve Prolapse (MVP)

❖ MVP is the commonest cause of subacute infective endocarditis in developed

❖ Causes of morbidity & mortality in Marfan syndrome:

❖ Describe the pathogenesis of acute MR

❖ Functional mitral regurgitation :

o Phase 3a – Rapid Repolarization

❖ Mechanism of uptake of calcium from cardiac myocyte before relaxation:

o Phase 4 – Spontaneous Depolarization

o Phase 0 – Rapid depolarization

o Phases 1 and 2 absent

❖ Wolff-Parkinson-White (WPW) Syndrome

❖ What is the “holiday heart syndrome”:

❖ Complete heart block → atrium is contracted by SA node, while ventricles

❖ ANP & BNP also ↓↓ renin secretion

❖ Additional mechanism of action of BNP : (+) protect against the

❖ Pulmonary capillary wedge pressure

❖ Commonest cardiac anomaly associated with Down syndrome :

❖ Complete Atrioventricular Canal Defect

❖ Clinical picture of late PDA:

❖ Patent Ductus Arteriosus (PDA) –

❖ Coarctation of the Aorta – aortic narrowing, types:

❖ Eisenmenger syndrome is due to pulmonary arterial hypertension → ↑↑

❖ Normal oxygenation pattern in the heart

❖ VSD murmur is usually cannot be heared at birth, audible around

❖ Fallout tetralogy murmur which is heared at the sternal border is

❖ Causes of cyanotic spells in TOF: dehydration, hyperventilation and mostly

❖ Causes & importance of Isolated systolic hypertension:

❖ Blood pressure changes in patient with Obstructive Sleep Apnea:

❖ L/M of hyaline arteriolosclerosis:

❖ DD; Malignant hypertension (extreme or rapidly developing hypertension) causes

❖ Fibrous cap in atheromatous plaque is formed by vascular smooth muscle cells

❖ Order of arteries affected in atherosclerosis :

❖ Second hold smoker (SHS) :

• It is caused by marfan syndrome , as it affect firillin-1 which is major ECM

❖ Pathogenesis of abdominal aortic aneurysm : all risk factors → ↑↑

❖ Traumatic aortic rupture occur in the aortic isthmus as it is tethered by

❖ Coronary steal phenomena :

❖ Biochemical changes & effect of ischemia in myocardium in 1 min:

❖ Describe process of ischemic preconditioning: brief repetitive