STEP 1
HyGuru
Learn. Integrate. Apply.
USMLE Step 1 Notes
Created by:
Rahul Damania, MD, David Shafran, MD
& the HyGuru community
CONTACT US:
513 484 5819
rahul@hyguru.com
Cleveland, OH
www.hyguru.com
Cardiovascular (CV)
QID
Topic
Educational Objective
HyGuru: A Step Beyond
System
Subject
Repeats
1623
Left atrial
enlargement
CV dysphagia can result from
external compression of the
esophagus by a dilated and
posteriorly displaced LA in pts w/
RHD and MS/MR.
Left atrial dilation can cause dysphagia Cardiovascular (CV)
• Rarely can compress left recurrent
laryngeal nerve
Anterior surface of heart
• Right atrium superiorly
• Right ventricle inferiorly
Anatomy (Anat)
1
1805
Varicocele
Cardiovascular (CV)
Pressure in the left renal vein may Right gonadal vein > IVC
become ↑ due to compression
•Left gondal vein > L renal vein > IVC
where the vein crosses the aorta
• L renal vein runs between SMA and
beneath the SMA. This
aorta (can be compressed) > varicocele
"nutcracker effect" can cause
hematuria and flank pain.
Pressure can also be ↑ in the left
gonadal vein, leading to
formation of a varicocele.
Anatomy (Anat)
1
1884
CT abdomen
The IVC is formed by the union The Superior Mesenteric Vein joins the Cardiovascular (CV)
of the right and left common iliac Splenic vein to form the Portal vein
veins at the lvl of L4-L5. The
renal arteries and veins lie at the
lvl of L1. The IVC returns venous
blood to the heart from the ↓
extremities, portal system, and
abdominal and pelvic viscera.
Anatomy (Anat)
1
1943
Brachiocephalic
vein obstruction
The BCV drains the ipsilateral
jugular and SCVs. The bilateral
BCVs combine to form the SVC.
BCV obstruction causes SSx
similar to those seen in SVC
syndrome, but only on one side of
the body.
Brachiocephalic vein obstruction
• Due to pancoast tumor or thrombotic
occlusion due to central line
• R side from subclavian and internal
carotid
• Ext carotid drains to subclavian
• R brachiocephalic vein drains R
lymphatic duct
• Right face and arm will be swollen
R subclavian or axillary obstruction
• R arm swelling only
SVC compression
• Bilaeral face, neck and arm swelling
Cardiovascular (CV)
Anatomy (Anat)
1
1967
CABG
The great saphenous vein is a
superficial vein of the leg that
originates on the medial side of
the foot, courses anterior to the
medial malleolus, and then travels
up the medial aspect of the leg
and thigh. It drains into the
femoral vein w/i the region of the
femoral triangle, a few cm
inferolateral to the pubic tubercle.
Cardiovascular (CV)
LAD block
• Left internal mammary artery is preferred
vessel for bypass
• Great saphenous vein with multiple
bypasses
• Superficial vein of leg
• Longest vein in body
• Med foot > ant to med malleolus >
med aspect of leg/thigh (3• 4cm
Inferolateral to pubic tubercle) > femoral
vein
• Accessed surgically near femoral
triangle (inguinal lig [sup], sartorius [lat],
adductor longus [med])
Baker's cyst can compress popliteal art
Small saphenous vein: lateral foot to
popliteal vein
Anatomy (Anat)
1
2130
Blunt aortic injury Traumatic aortic rupture is most
often caused by the rapid
deceleration that occurs in MVCs.
The most common site of injury
is the aortic isthmus, which is
tethered by the ligamentum
arteriosum and is relatively fixed
and immobile compared to the
adjacent descending aorta.
Cardiovascular (CV)
Anatomy (Anat)
1
Blunt aortic trauma (sudden
deceleration)
• Aortic isthmus (tethered by ligamentum
arteriosum) is more commonly ruptured
• Can affect ascending aorta but is rare
7646
Implantable
cardioverter
defibrillator
LV leads in biventricular PMs
course through the coronary
sinus, which resides in the AV
groove on the posterior aspect of
the heart.
Cardiovascular (CV)
Biventricular pacemaker 3 leads
• 1 in RA, 1 in RV
• 1 in LV via the Ra > coronary sinus (via
atrioventricular groove on posterior heart)
> lateral venous tributaries into LV
Anatomy (Anat)
1
11730
Sinoatrial node
The SA node consists of
specialized PM cells located at
the jxn of the RA and SVC. It is
the site of earliest electrical
activation in pts w/ sinus rhythm.
Cardiovascular (CV)
SA node
• Junction of right atrium and SVC
AV node
• Right atrium near septal cusp of tricupsid
valve near coronary sinus
Anatomy (Anat)
1
11832
Retinal artery
occlusion
RAO is a cause of acute, painless,
monocular vision loss. It is
usually caused by TE
complications of atherosclerosis
traveling from the ICA and
through the ophthalmic artery.
Internal carotid > opthalmic artery >
retinal artery
• Retinal artery occlusion: painless vision
loss with cherry red spot on macula
Cardiovascular (CV)
Anatomy (Anat)
1
11956
AV node
The AV node is located on the
endocardial surface of the RA,
near the insertion of the septal
leaflet of the TV and the orifice
of the coronary sinus.
AV node is located near the insertion of Cardiovascular (CV)
the septal leaflet of the tricupsid valve
and the orifice of the coronary sinus
• Opening of the pulmonary vein is the
MC location of ectopic A Fib generation
• Isthmus between the IVC and
tricuspid annulus is site of ablation for A
Flutter
SA node is located in the upper right
anterior portion near the opening for the
SVC
Anatomy (Anat)
1
12046
Subclavian steal
syndrome
Subclavian steal syndrome occurs
due to severe stenosis of the
proximal SCA, which leads to
reversal in blood flow from the
contralateral vertebral artery to
the ipsilateral vertebral artery. Pts
may have SSx related to arm
ischemia in the affected extremity
(eg, exercise-induced fatigue,
pain, paresthesias) or
vertebrobasilar insufficiency (eg,
dizziness, vertigo).
Cardiovascular (CV)
Anatomy (Anat)
1
654
Penetrating
thoracic trauma
The LV forms the apex of the
heart and can reach as far as the
5th ICS at the left MCL. All other
chambers of the heart lie medial
to the left MCL. The lungs
overlap much of the anterior
surface of the heart.
Cardiovascular (CV)
Stab in 5th intercostal space at the
midline in lateral direction will
penetrate the left lung
• Lung extend above 1st rib
• Stab wound more medial and deeper
could hit the left ventricle (anterior surface
covered by the lung)
• Apex at midclavicular line
Heart
• Anterior surface: RV
• Inferior surface: RV + LV touching
central tendon
• Posterior surface: LA
Azygos vein
• Posterior mediatinum immediately to the
right of the midline
Anatomy (Anat)
2
1699
Penetrating
thoracic trauma
The RV composes most of the
heart's anterior surface. A deep,
penetrating injury at the left
sternal border in the 4th ICS
would puncture the RV.
Stab wound to 4th intercostal left sternal Cardiovascular (CV)
body
• Skin
• Pec major
• Ext intercostal
• Internal intercostal
• Internal thoracic art and vein
• Trasversus thoracis muscle
• Parietl pleura
• Pericardium
• R ventricle
Stab to the right of the vertebral body from
behind could injury IVC
Stab to 2nd intercostal left sternal border
could injure pulmonary trunk
L atrium: posteriod surface of heart L
ventricle: lateral surface of heart
Anatomy (Anat)
2
2023
Central venous
catheter
The common cardinal veins of the
developing embryo drain directly
into the sinus venosus. These
cardinal veins ultimately give rise
to the SVC and other constituents
of the systemic venous
circulation.
Cardiovascular (CV)
Central line
• Subclavian or internal jugular vein
• SVC comes from common cardinal veins
which drain into the sinus venosus
Embryonic veins
• Umbical > ligamentum teres hepatis
• Vitellin > portal system
• Cardinal >sinus venosus > SVC
Anatomy (Anat)
2
8332
Echocardiography The LA forms the majority of the TEE
posterior surface of the heart and • Pointed anteriorly: left atrium, atrial
resides adjacent to the esophagus. septum and mitral valve
Enlargement of the LA can
compress the esophagus and
cause dysphagia.
Cardiovascular (CV)
Anatomy (Anat)
2
8333
Echocardiography The descending thoracic aorta lies
posterior to the esophagus and the
LA. This position permits clear
visualization of the descending
aorta by TEE, allowing for the
detection of abnormalities such as
dissection or aneurysm.
Anatomy (Anat)
2
11763
Central venous
catheter
The femoral triangle (lateral to
medial) consists of the femoral
nerve, femoral artery, femoral
vein, and deep inguinal
nodes/lymphatic vessels.
Cannulation of the femoral vein
should occur approximately 1 cm
below the inguinal ligament and
just medial to the femoral artery
pulsation.
Cardiovascular (CV)
TEE
• If pointed posteriorly: will see descending
aorta
RALS
• Right pulmonary artery is Anteriot to
bronchi Left pulmonary artery is Superior
to bronchi
SVC
• Formed behind right 1st costal cartilage
• Compressed by pancoast tumor or
mediastinal mass
Cardiovascular (CV)
Femoral vein
• Just medial to femoral art (1 cm below
inguinal ligament, 0.5• 1 cm medial to
femoral art)
• NAVEL from lat to med
Anatomy (Anat)
2
11764
Cardiac
catheterization
The optimal site for obtaining
vascular access in the lower
extremity during cardiac
catheterization is the common
femoral artery below the inguinal
ligament. Cannulation above the
inguinal ligament can
significantly ↑ the risk of
retroperitoneal hemorrhage.
Anatomy (Anat)
2
11780
Pulmonary blood
flow
Anatomy (Anat)
2
Cardiovascular (CV)
Cardiac Cath
• Cath into femoral or radial artery
• Middle of hip below inguinal lig
• Arterial puncture ABOVE the inguinal
ligament increases risk for retroperitoneal
hemorrhage
• Cannot be controlled by manual
pressure
• Present with hemodynamic instaibility,
hypotension
Right paracolic gutter (between ascending
colon and abdominal wall): fluid
accumulation > think GI organ issue
Cardiovascular (CV)
PAOP is measured at the distal tip Swan Ganz Catheter
of the pulm artery catheter after • Catheter inserted into pulmonary artery >
an inflated balloon occludes
balloon infilated > measure P (PCWP =
blood flow through a pulm artery LA and LV end diastolic pressure)
branch. It closely corresponds to Pleural manometry
LA and LV EDP.
• Catheter placed into pleural space and
measures pleural pressure
15197
Cardiac
catheterization
To access the left side of the
heart, CVCs must cross the
interatrial septum at the site of the
foramen ovale. Entry into the LA
allows for direct measurement of
LA pressure and for access to
arrhythmogenic foci on the LA
myocardium or pulm veins.
Cardiovascular (CV)
Anatomy (Anat)
2
8294
Tricuspid
regurgitation
IE in IVDUs commonly affects
the TV, often leading to septic
pulm emboli. Pts can have an
early- or holo-systolic murmur of
TR, which is best auscultated in
the 4th or 5th ICS at the left
lower sternal border.
Cardiovascular (CV)
Anatomy (Anat)
3
1751
Patent ductus
arteriosus
The ductus arteriosus is derived
from the sixth embryonic aortic
arch. A patent ductus arteriosus
(PDA) causes left-to-right
shunting of blood that can be
heard as a continuous murmur
over the left infraclavicular
region. Indomethacin (a PGE2
synthesis inhibitor) can be used to
close a PDA in premature infants,
but surgical ligation is often
necessary in older patients.
Aortic Arch Derivatives 1: maxillary art Cardiovascular (CV)
• stapedius art, hyoid art
• common carotid, prox part of internal
carotid
• left > aortic arch; right > prox part of R
subclavian art 6: left > ductus arteriosus;
right > prox pulmonary art
Anatomy (Anat)
4
11831
Coronary artery
disease
The inferior epigastric artery is 1
of 2 branches of the external iliac
artery and takes off immediately
proximal to the inguinal ligament.
It provides blood supply to the
lower anterior abdominal wall as
it runs superiorly and medially up
the abdomen.
Cardiovascular (CV)
External iliac art
• Gives off Inf Epigastric art (runs sup and
med into abdomen)
• Gives off Deep Circumflex Iliac artery
(also supplies lower abdominal wall)
• Becomes common femoral artery once it
passes the inguinal ligament
Medial circumflex femoral artery
• Branch of Deep Femoral
• Supplies femoral neck/head
Anatomy (Anat)
4
11842
Atrial fibrillation
AF is a/w ↑ risk of systemic TE.
The LA appendage is the most
common site of thrombus
formation.
Cardiovascular (CV)
A fib
• Risk of systemic thromboembolism due
to stasis
• Left atrial appendage is MC site for clot
Crista terminalis: separates smooth sinus
venosus and pectinate muscles
LV mural thrombus: systolic dysfunction >
impaired apical wall movement
Anatomy (Anat)
5
12151
Aortic dissection
The intimal tear in Stanford type
A AD (involving the ascending
aorta) usually originates in the
sinotubular jxn whereas the
intimal flap in Stanford type B
AD usually starts near the origin
of the left SCA. Dissections can
propagate distally to the
thoracoabdominal aorta.
Cardiovascular (CV)
Anatomy (Anat)
6
1871
Coronary blood
flow
The inferior wall of the LV forms
most of the inferior
(diaphragmatic) surface of the
heart and is supplied by the PDA.
In 85%-90% of individuals, the
PDA derives from the RCA (right
dominant coronary circulation).
Cardiovascular (CV)
Anatomy (Anat)
9
RCA
• Posterior descending art in 90% of pop
• PDA controls AV node
• Occlusion > inferior wall infarct
LAD
• Give off diagonal branch
• Supplies anterior papillary muscle
Left circ
• Lateral wall of LV
Right marginal
• From RCA
• Supplies RV
11837
Coronary blood
flow
Coronary dominance is
Coronary Dominance
determined by the coronary artery • Determined by which artery supplies
supplying the PDA. The PDA
PDA
originates from the RCA in
• RCA 70% of time
approximately 70%-80% of pts
• Left circ 10% of time
(right dominant), both the RCA
• Codominant 20% of time
and LCX in 10%-20%
LAD: supply anterior 2/3 of septum and
(codominant), and the LCX in 5%- ant wall of LV Left diagonal: branch of
10% (left dominant). The
LAD and supplies lat wall of LV
dominant coronary artery supplies Right marginal: branch of RCA and
blood to the AV node via the AV supplies free wall of RV
nodal artery.
Cardiovascular (CV)
Anatomy (Anat)
9
1538
Pulmonary
embolism
The IVC courses through the
abdomen and inferior thorax in a
location anterior to the right half
of the vertebral bodies. The renal
veins join the IVC at the lvl of
L1/L2, and the common iliac
veins merge to become the IVC at
the lvl of L5. IVC filters are
placed in pts w/ DVT who have
c/i to anticoagulation Thx.
IVC filter: prevents the propagation of
DVT from the legs to the lungs
• Used in pt with contraindication to
anticoagulation Renal veins join IVC at
L1/L2
Common iliac veins becomes IVC at L4
Cardiovascular (CV)
Anatomy (Anat)
13
10467
Myocardial
infarction
Leads I and aVL correspond to
the lateral limb leads on ECG.
Therefore, ST elevation or Q
waves in these leads are
indicative of infarction involving
the lateral aspect of the left
ventricle, which is supplied by the
left circumflex artery.
STEMI
1 and avL
• Lateral infarct > L circumflex
V1 V4
• Anterior infart > LAD
• Distal LAD in V3 and V4
V1 V6+1+avL
• Left main coronary artery
2,3 and avF
• Inferior infarct
Cardiovascular (CV)
Anatomy (Anat)
18
12144
Myocardial
infarction
Papillary muscle rupture is a lifethreatening complication that
typically occurs 3-5 days after MI
and presents w/ acute MR and
pulm edema. The posteromedial
papillary muscle is supplied
solely by the PDA, making it
susceptible to ischemic rupture.
Cardiovascular (CV)
Anatomy (Anat)
18
1883
Community
acquired
pneumonia
On posteroanterior chest x-ray,
the right middle lobe is seen
adjacent to the right border of the
heart, which is primarily formed
by the right atrium. Consolidation
in the right middle lobe can
obscure the X-ray silhouette of
the right heart border.
• RA: most of right side cardiac silhouette Cardiovascular (CV)
IVC: most inferior edge of right border
• Pulmonary art: left side of silhouette just
below aortic arch RV: anterior wall
• SVC: flattened opacity parallel to
vertebral column that
terminates inferiorly at RA
Anatomy (Anat)
21
788
Homocysteine
↑ lvls of plasma homocysteine are
an independent RFx for
thrombotic events. Homocysteine
can be metabolized to methionine
via remethylation or to
cystathionine via transsulfuration.
Hyperhomocysteinemia is most
commonly due to genetic
mutations in critical enzymes or
deficiencies of vitamin B12,
vitamin B6, and folate.
Cardiovascular (CV)
Homocysteine to Methionine
(Methionine synthase + methylene
tetrahydrofolate reductase + B9,12)
Methionine to SAM
• Homocysteine to cystathionine
(cystathionine synthase + B6)
Cystathionine to Cysteine (Cystathionase +
B6)
Homocystinuria
• Increased risk for athero (damages
endothelial cells)
B12 deficiency
• Lethargy, seizures, paresthesias and
hypotonia due to MMA
Biochemistry
(Bioc)
2
1047
Dilated
cardiomyopathy
Thiamine deficiency causes
beriberi and Wernicke-Korsakoff
syndrome. Dry beriberi is
characterized by symmetrical
peripheral neuropathy; wet
beriberi includes the addition of
high-output congestive heart
failure.
Cardiovascular (CV)
Thiamine def
• Beriberi: peripheral neuropathy and
dilated cardiomyopathy
• Can occur in less than 1 year of poor
intake (help to differentiate between B12
def)
• Infantile will present 2• 3months after
birth
Riboflavin def
• Angular cheilosis, stomatitis, glossitis
• Normocytic anemia
Vit A def
• Increased risk for measels (explains why
this is a tx)
Cardiovascular (CV)
Southern blotting is a technique x linked recessive
used to identify DNA mutations. • Father to son does not occur
It involves restriction
Southern blot for DNA
endonuclease digestion of sample • DNA extracted
DNA, gel electrophoresis, and
• Restriction endonuclease
gene identification w/ a labeled
• Gel electrophoresis
DNA probe.
• DNA probe to identify target DNA
2034
Southern blotting
1229
Sensitivity and
specificity
When undergoing Dx testing, pts • True positive = (sensitivity) x (# of pt
actually with dz) False negative = (1•
w/ the disease can test (+) (true
(+), TP) or (-) (false (-), FN). The sensitivity) x (# of pt actually with dz)
sensitivity of a test determines the
proportion of pts that are
correctly classified:
TP = (Sensitivity) x (Number of
pts w/ the disease)
FN = (1 - Sensitivity) x (Number
of pts w/ the disease)
1283
Comparing 2
means
1301
35
Biochemistry
(Bioc)
8
Biochemistry
(Bioc)
1
Cardiovascular (CV)
Biostatistics (Bios) 4
The two-sample t test is a
statistical method commonly
employed to compare the means
of 2 groups of subjects.
t test: comparing 2 means of populations Cardiovascular (CV)
• Calculate p value
• P value < 0.05: reject null (the groups are
statistically significantly different)
Linear regression
• Model linear relationship between a
dependent variable and an independent
variable
Correlation coefficient: measure of strenfth
and direction of a linear relationship
between 2 variables
Chi squared: comparing 2 categorical data
Meta analysis: used to increase power
Biostatistics (Bios) 1
Bias
The main purpose of blinding is
to prevent pt or researcher
expectancy from interfering w/ an
outcome.
Double blinding
• Prevents observer bias
Beta error
• Concludes no difference when there is
one
Recall bias
• Inaccurate recall usually seen with dz
• Seen in case control studies
Selection bias
• People are non randomly selection or
from the selective loss of follow up
Cardiovascular (CV)
Biostatistics (Bios) 4
Transposition of
the great vessels
An echocardiogram showing an
aorta lying anterior to the
pulmonary artery is diagnostic of
transposition of the great arteries
(TGA). This life-threatening
cyanotic condition results from
failure of the fetal
aorticopulmonary septum to spiral
normally during septation of the
truncus arteriosus.
Cardiovascular (CV)
Transposition of the Great Arteries
• Failure of aorticopulmonary septum to
spiral
• Will see anterior lying aorta
• Must have a shunt to live (ASD, PDA,
PFO, VSD)
• Associated with maternal diabetes
Random
Syndactyly: failure of apoptosis
Hypospadias: failure of fusion
Branchial cleft cyst: failure of obliteration
VSD: failure of interventricular septum to
proliferate Trunuc arteriosus: failure of
septation
Embryology
(Embr)
1
202
1705
Atrial septal defect The foramen ovale is patent in
approximately 25% of normal
adults. Although the foramen
ovale usually remains fxnally
closed, transient ↑ of RA pressure
above LA pressure can produce a
right-to-left shunt, leading to
paradoxical embolism of venous
clots into the arterial circulation.
Cardiovascular (CV)
Cryptogenic (paradoxical) Stroke
• DVT > PFo > stroke
PFO
• Failure or septum primum and septum
secundum to fuse
ASD
• Absence of either septum primum or
secundum to develop
• Can cause HF, pulmonary HTN or
Eisenmenger
• Fixed S2 splitting
Truncus arteriosus
• Incomplete development of
aorticopulmonary septum
VSD
• Incomplete closure of interventricular
foramen
Cardiovascular (CV)
Tetralogy of Fallot TOF results from anterior and
TOF
cephalad deviation of the
• Abnormal neural crest cell migration >
infundibular septum during
anterior and cephalad deviation of
embryologic development,
infundibular septum
resulting in a malaligned VSD w/
• RV outflow tract obstruction can be
an overriding aorta. As a result. subvalvular, intravalvular or supravalvular
the pt has RV outflow obstruction TAPVR
(resulting in a systolic murmur) • All blood back to Ra > must have ASD
and squats to ↑ the peripheral
or VSD
SVR (afterload) and ↓ right-toFailed Fusion of Sup and Inf endocardial
left shunting across the VSD.
cusion
• Can lead to Eisenmenger syndrome
Embryology
(Embr)
2
Embryology
(Embr)
3
1750
Embryologic
derivatives
The 1st AA gives rise to a portion
of the maxillary artery, and the
2nd AA gives rise to the stapedial
artery, which typically regresses
in humans. The 5th AA
completely regresses, leaving no
structures or vestiges in the adult.
The 3rd AA forms the CCAs and
proximal ICAs. The 4th AA gives
rise to part of the true AA and a
portion of the SCAs. The 6th AA
gives rise to the pulm arteries and
the ductus arteriosus.
Cardiovascular (CV)
Pharyngeal Arch
• CN 5, maxillary art
• CN 7, stapedius art (typically regresses)
• CN 9, Common carotid art and prox
internal carotid art 4: Superior laryngeal
nerve, L aorta; r subclavian art 6:
Recurrent laryngeal nerve. L ductus
arteriosus; r pulmonary art
Embryology
(Embr)
2
30
Turner syndrome
Aortic coarctation in a
child/young adult presents with
lower-extremity claudication (eg,
pain and cramping with exercise),
blood pressure discrepancy
between the upper and lower
extremities, and delayed or
diminished femoral pulses.
Turner syndrome (45,XO) is
associated with coarctation of the
aorta in up to 10% of cases.
Cardiovascular (CV)
Heart Dz Down
• Endocardial cushion (ostium primum, AV
regurg)
DiGeorge
• TOF
• Truncus arteriosus
• Interrupted aortic arch: aortic arch is
atretic or segment absent, low BP in legs,
respiratory distress, CHF on 1 day of life
Freidreich
• HCM
Kartagener
• Situs inversus
Marfan
• Cystic medial necrosis (aortic
dissection/aneurysm)
• MVP
TS
• Ventricular rhabdomyoma
Turner
• Aortic coarc
• Infantile: cyanosis of leg (patent PDA)
• Adult: BP variable, rib notching
• Bicuspid aortic
Genetics (Gene)
8
Cardiovascular (CV)
Down Syndrome
• 95%: Meitotic nondisjunction
• 5%: Robertsonian translocation (14 and
21)
• 1% mosiascism
• Flat face, epicanthal folds, upslanting
palpebral fissures, protruding tongue, small
ears, endocardial cushion heart defects
Chromosomal deletions
• Cri du chat: 5p
• DiGeorge: 22q11
Imprinting
• Prader willi
Cardiovascular (CV)
TS is a/w congenital anomalies of Turner's
the aorta, and the most common • Short stature, webbed nick, broad chest,
defect is a bicuspid AV. A
shortened fourth metacarpal
nonstenotic bicuspid AV can
• Bicuspid aortic valve and pre ductal
MFx as an early systolic, highcoarctation
frequency click over the right 2nd
• Early systolic, high frequency click
interspace. Bicuspid AVs are at
• Increased risk of stenosis, insufficienc
risk for stenosis, insufficiency,
and infection
and infection.
Downs
• Complete atrioventricular canal, ASD and
VSD
Rheumatic heart disease
• MR early, MS late
Marfans, Ehlers Danlos, Fragile X
• MVP
PDA
• Premature baby, rubella
Genetics (Gene)
6
Genetics (Gene)
8
Cardiovascular (CV)
Genetics (Gene)
8
Cardiovascular (CV)
Type 1 Collagen
• Dermis, bone, tendon, ligaments, dentin,
cornea, scar tissue
Type 2 Collagen
• Cartilage, vitreous humor, nucleus
pulposus
Type 3 Collagen
• Skin, lungs, intestines, blood vessels,
bone marrow, lymphatics and granulation
tissue
Type 4 Collagen
• Basement membrane
Cardiovascular (CV)
Acute transplant rejection
• Weeks after surgery
• Dense infiltrate of mononuclear cells
(mainly T cells)
• T cell sensitization against graft MHC Ag
Hyperacute rejection
• Cessation of blood flow immediately
Hypersensitivity myocarditis
• Perivascular infiltrate with abundant
eosinophils
Chronic rejection
• Scant inflammatory cells with interstitial
fibrosis
Histology (Hist)
1
Immunology
(Immu)
1
Microbiology
(Micr)
15
882
Down syndrome
DS is most commonly caused by
maternal meiotic nondisjxn, a
process by which the fetus
receives 3 full copies of
chromosome 21. Dysmorphic
features (eg, flat facial profile,
protruding tongue, small ears,
upslanting palpebral fissures) and
cardiac defects (eg, endocardial
cushion defects) are Chx.
8292
Turner syndrome
13600
Dilated
cardiomyopathy
AD mutations in the TTN gene,
which encodes for the sarcomere
protein titin, are the most
common cause of familial DCM.
8711
Collagen types
Type I collagen is the most
prevalent collagen in the human
body and is the 1° collagen in
mature scars.
568
Heart
transplantation
Acute cardiac transplant rejection
occurs wks following
transplantation and is primarily a
cell-mediated process. On
histopathologic analysis of an
endomyocardial Bx, a dense
mononuclear lymphocytic
infiltrate w/ cardiac myocyte dmg
will be visualized. Tx w/
immunosuppressive Rx is aimed
primarily at preventing this form
of rejection.
679
Endocarditis
Staphylococcus epidermidis, a
Gram (+) coccus that grows in
clusters, is a skin commensal that
is a common cause of infection in
pts w/ prosthetic devices such as
artificial joints or heart valves.
Unlike S aureus, S epidermidis is
coagulase (-). Unlike S
saprophyticus (another coagulase
(-) staphylococci species), S
epidermidis is susceptible to
novobiocin.
Cardiovascular (CV)
729
Endocarditis
Staphylococcus aureus causes
acute BE w/ rapid onset of SSx,
including shaking chills (rigors),
high fever, dyspnea on exertion,
and malaise. In IVDUs, it can
cause right-sided endocarditis w/
septic embolization into the
lungs.
Cardiovascular (CV)
Microbiology
(Micr)
15
733
Endocarditis
Enterococcus is a component of
the normal colonic and urogenital
flora and is capable of growing in
hypertonic saline and bile. It is γhemolytic, catalase (-), and
pyrrolidonyl arylamidase (+). GU
instrumentation or catheterization
has been a/w enterococcal
endocarditis.
Cardiovascular (CV)
Microbiology
(Micr)
15
1001
Endocarditis
Streptococcus gallolyticus
(formerly S bovis) endocarditis
and bacteremia are a/w GI lesions
(colon ca) in ~25% of cases.
When S gallolyticus is cultured in
the blood, workup for colonic
malignancy w/ colonoscopy is
essential.
Cardiovascular (CV)
Microbiology
(Micr)
15
1002
Endocarditis
Viridans streptococci produce
dextrans that aid them in
colonizing host surfaces, such as
dental enamel and heart valves.
These organisms cause subacute
BE, classically in pts w/ preexisting cardiac valvular defects
after dental manipulation.
Cardiovascular (CV)
Microbiology
(Micr)
15
1003
Endocarditis
Viridans streptococci are normal Dental cleaning > bacterial endocarditis Cardiovascular (CV)
inhabitants of the oral cavity and due to Viridans streptococci > dextrans
are a cause of transient
bind to fibrin and platelets
bacteremia after dental
• MVP does not significantly increase
procedures in healthy and
your risk for subacte endocarditis
diseased individuals. In pts w/ pre- Subendothelial collagen is important for
existing valvular lesions, viridans platelet adhesion, not bacterial
streptococci can adhere to fibrinplatelet aggregates and establish
infection that leads to
endocarditis.
Microbiology
(Micr)
15
8282
Catheter related
bloodstream
infection
The most important steps for
prevention of CVC infections are
as follows:
Proper hand hygiene
Full barrier precautions during
insertion
Chlorhexidine skin disinfection
Avoidance of the femoral
insertion site
Removal of the catheter when it
is no longer needed
Cardiovascular (CV)
Central Venous Catheter
• S Aureus and S epi are common
infections
Reduction in CVC infection
• Hand watching
• Chlorhexidine skin disinfection
• Sterile procedure
• Subclavian or internal jegular insertion >
femoral
• Remove ASAP
Microbiology
(Micr)
3
Staph Aureus Endocarditis (IV drug
user)
• Perforate heart valves, rupture chordae
tendineae, send septic emboli to lung or
brain
Candida endocarditis
• 3rd MCC if IV drug user
Culture negative endocarditis
• HACEK
• Haemophilus, Actinobacillus,
Cardiobacterium, Eikenella, Kingella
Strep Gallolyticus (bovis)
• Endocarditis + colon cancer
Enterococcus
• Gram +, cat neg, grows in hypertonic
saline and bile, PYR positive, gamma
hemolytic
• Can cause endocarditis after cytscopy,
colonoscopy, and obstetric procedures
Viridans Strep
• Dental procedures
Corynebacterium, Haemophilus, Staph,
Strep, Neisseria
• Bactermia after nasal polyp removal
Viridans Streptococci
• Strep Mutans and Step Sanguinis
• Cause dental caries
• Cause subacute bacterial endocarditis,
deep wound infections, abdominal
abscesses and septicemia
• Dextrans adhere to tooth enamel and
fibrin platelet aggregates
Anterior Uveitis
• HSV, Syphilis, Lyme disease
• HLa B27
Erythema nodosum
• GAS, S Aureus, cocci, histo, blasto,
chlamydia, crohns, sarcoid
31
Aortic coarctation Pts w/ adult-type coarctation of
the aorta commonly die of HTNassoc complications, incl LV
failure, ruptured dissecting AA,
and SICH. These pts are at ↑ risk
for ruptured intracranial
aneurysms b/c of the ↑ incidence
of congenital BAs of the COW as
well as aortic arch HTN.
Spontaneous Intracranial Hemorrhage
• AVM, ruptured cerebral aneurysms,
abuse of cocaine
• Can also be due to coaractation of the
aorta
Cardiovascular (CV)
Pathology (Path)
1
32
Patent ductus
arteriosus
Digital clubbing and cyanosis w/o
BP or pulse discrepancy are
pathognomonic for a large PDA
complicated by Eisenmenger
syndrome (reversal of shunt flow
from L-R to R-L). Severe
coarctation of the aorta can cause
lower extremity cyanosis. R-L
shunting in pts w/ large septal
defects and TOF results in wholebody cyanosis.
Cardiovascular (CV)
PDA
• Large PDA can lead to Eisenmenger
syndrome > cyanosis and clubbing in lower
extremities WITHOUT pressure difference
from upper to lower extremities
Coarctation of aorta
• Infant: cyanosis of lower extremities
• Adults: pressure difference between
upper and lower extremities, rib notching
ASD and VSD that become Eisenmenger
syndrome
• Cyanosis of upper and lower body
equally
TOF
• Whole body cyanosis
Pathology (Path)
4
36
Atherosclerosis
Stable angina pectoris results
from myocardial O2 demandsupply mismatch and MFx as
chest pressure, tightness, or pain
that is reliably produced by
exertion and relieved by rest. It
most commonly occurs due to a
fixed atherosclerotic plaque
obstructing >70% of the coronary
artery lumen that limits blood
flow during exertion.
Cardiovascular (CV)
Stable Angina
• 75%+ occlusion of the coronary artery is
necessary
Unstable Angina or non STEMI
• Ulcerated athero + partial thrombi
occulsion
Prinzmetal
• May occur at rest
Pathology (Path)
8
37
Myocardial
infarction
STEMI involves transmural (fullthickness) infarction of the
myocardial wall, and usually
results from acute atherosclerotic
plaque rupture w/ the devel of
overlying thrombus that fully
occludes the coronary artery
lumen. It classically presents w/
sudden-onset substernal chest
pain that's not relieved by rest or
short-acting nitrates. ECG
demonstrates STE in the affected
leads w/ subseq devel of Q
waves.
Acute MI
Cardiovascular (CV)
• typical chest pain not relieved by rest or
nitroglycerin, diaphoresis, nause,
palpitation
• Peaked T waves (localized hyperK)
• STEMI
• Q waves
• MCC by plaque rupture with
superimposed thrombus completely
occluding the coronary artery
Random
Stable angina: 75% occlusiong of coronary
artery
Unstable angina: ulcerated atherosclerotic
plaque with partially occluding thrombus
Prinzmetal: coronary artery spasm (ST
elevation)
• Usually responds to nitro
Pathology (Path)
18
39
Atherosclerosis
Gradually developing myocardial
ischemia encourages the
formation and maturation of
collateral vessels and is most
likely to occur in the setting of a
slow-growing, stable
atherosclerotic plaque. An
unstable atherosclerotic plaque
(eg, that w/ active inflammation,
a lipid-rich core, a/o a thin fibrous
cap) is more likely to rupture,
resulting in the abrupt onset of
ischemia/infarction that precludes
the development of viable
collateral vessels.
Cardiovascular (CV)
Rate of arthero formation is most
important in determining ischemic
damag
• Slowly progressing coronary artery athero
> arterial collateral circulation around
occlusion
• Fibrous cap over athero plaque thins >
risk of rupture Larger lipid rich core of
athero > risk of rupture
• Macrophages secrete metalloproteinase
which thin fibrous cap of athero
Statins decrease inflammation of athero >
stabilzes plaque
• More calcification of coronary artery >
the greater the risk of rupture
Pathology (Path)
8
40
Myocardial
infarction
After the onset of severe ischemia
leading to MI, early signs of coag
necrosis don't become apparent
on LM until 4hrs after the onset
of MI.
Cardiovascular (CV)
MI
0 4hr: no change
4 12: early coag nec, edema, wavy fibers
• Cytoplasmic hypereosinophilia
12 24: coag nec, contraction band necrosis
15day: coag nec and neutrophils
510day: macrophage
10 14day: granulation tissue and
neovascularization 2wk 2mnth: collagen
deposition/scar
Pathology (Path)
18
43
Myocardial
infarction
Hibernating myocardium refers to
the presence of LV systolic
dysfxn due to ↓ coronary blood
flow at rest that's partially or
completely reversible by coronary
revascularisation.
Cardiovascular (CV)
• Myocardial hibernation: chronic
myocardial ischemia that lowers
myocardial metabolism and function to
match blood flow preventing necrosis.
Disorganized contractile and
cytoskeletal proteins, altered adrenergic
contril and increased Ca2+ response >
decreased contraction. Coronary
revascularization and return of flow will
improve contractility and LV function.
• Ischemic preconditioning: repeated brief
ischemic events protect myocardium from
subseqent prolonged ischemia
Pathology (Path)
18
72
Endocarditis
Janeway lesions are nontender,
macular, and erythematous
lesions typically located on the
palms and soles of pts w/ acute IE
and are the result of septic
embolization from valvular
vegetations.
Cardiovascular (CV)
Infective Endocarditis Vascular issue
• Systemic emboli > cerebral, pulmonary or
splenic
• Mycotic aneurysm
• Janeway (painless on palms and soles)
Immunologic issue
• Osler (painful on fingertips and toes)
• Roth spots
Pathology (Path)
15
73
SLE
CV MFx of lupus include
accelerated atherosclerosis, smallvessel necrotizing vasculitis,
pericarditis, and Libman-Sacks
endocarditis (small, sterile
vegetations on both sides of the
valve). Renal involvement
classically MFx as DPGN, which
is Chx by diffuse thickening of
the glomerular capillary walls w/
"wire-loop" structures on LM.
SLE
• Hypercoag > likely to cause MI
• Lidman Sacks (verrucous) endocarditis
• Sterile vegetations of both sides of the
valve > can cause regurg or stenosis
Dermatomyositis
• Extramuscular: interstitial lung disease,
vasculitis and myocarditis
Cardiovascular (CV)
Pathology (Path)
7
74
Carcinoid tumors
Carcinoid syndrome typically
presents w/ episodic flushing,
secretory diarrhoea, and
wheezing. It can lead to
pathognomonic plaque-like
deposits of fibrous tissue on the
right-sided endocardium, causing
TR and right-sided HF. ↑ 24-hr
urinary 5-HIAA can confirm the
Dx.
Cardiovascular (CV)
Carcinoid Syndrome
• Flushing, diarrhea and bronchospasm
• TIPS (Tricupsid Insufficiency, Pulmonary
Stenosis) due to serotonin stimulating
fibroblast growth > plaque like fibrous
tissue deposits on endocardium
• High 5• HIAA
• CT/MRI to locate tumor
• Tx: octreotide and surgery
Carcinoid tumor
• Can secrete histamine, serotonin and VIP
Hyperhomocysteinemia
• Arterial or venous thrmbosis and
atherosclerosis
Pathology (Path)
4
76
Hypertrophic
cardiomyopathy
In pts w/ HCM, dynamic LVOT
obstr is due to abn systolic
anterior motion of the anterior
leaflet of the MV toward a
hypertrophied IV septum.
HCM
• LV outflow obstruction due to anterior
motion of mitral valve toward the
interventricular septum during systole
• Harsh systolic crescendo decrescendo
murmur > worsens
with valsalva, standing up or nitro
Cardiovascular (CV)
Pathology (Path)
9
82
Hypertrophic
cardiomyopathy
HCM is a common cause of SCD
in young adults. Histologic
features incl cardiomyocyte
hypertrophy and myofiber
disarray w/ ↑ interstitial fibrosis.
The structural disarray creates a
substrate for ventricular
arrhythmia (e.g. v-tach, VF) that
can lead to SCD.
Cardiovascular (CV)
Endocardial thickening and
noncompliant ventricular walls:
restrictive cardiomyopathy
• Amyloid, sarcoid, endomyocardial
fibrosis, Leoffler's
Patchy fibrosis in the mural endocardium:
chronic ischemic heart disease
Pathology (Path)
9
83
Hypertrophic
cardiomyopathy
HCM is Chx by asymmetric (eg,
septal) LVH that can result in
SCD. AD mutations affecting the
cardiac sarcomere genes (eg,
cardiac β-myosin heavy chain
gene and myosin-binding protein
C gene) are responsible for the
majority of cases.
Cardiovascular (CV)
HCM
• Missense mutation in beta myosin heavy
chain and myosin binding protein C
Marfans
• fibrillin 1 mutation on chromosome 15
K+ cardiac channel protein mutations:
congenital long QT > increased risk of
Torsades
Mutated transthyretin: cardiac amyloidosis
Pathology (Path)
9
84
Long QT
syndrome
Unprovoked syncope in a
previously aSSx young person
may result from a congenital
LQTS. The 2 most important
congenital syndromes w/ QT
prolongation — RWS and JLNS
— are thought to result from muts
in a K+ channel protein that
contributes to the delayed rectifier
current (IK) of the cardiac AP.
Cardiovascular (CV)
Congenital prolonged QT
• Mutations in K channel (internal rectifier)
JervelL Lange Nielson
• AR
• Neurosensory deafness
Romano Ward
• AD
• No hearing issue
Dilated CM
• Mutation of cytoskeleton or mitochondria
HCM
• Mutatio in beta myosin heavy chain
Arrhythmogenic Right Ventricular
Cardiomyopathy
• Mutation of Ca binding sarcoplasmic
reticulum protein
• Progressive fibrofatty change in
myocardium
Pathology (Path)
4
86
Long QT
syndrome
Congenital LQTS is most often
caused by genetic muts in a K+
channel protein that contributes to
the outward-rectifying K+
current. A ↓ in the outward K+
current leads to prolongation of
AP duration and QT interval.
This prolongation predisposes to
the devel of life-threatening
ventricular arrhythmias (e.g. TdP)
that can cause palpitations,
syncope, seizures, or SCD.
Cardiovascular (CV)
Congenital long QT syndrome
• Decrease K efflux (internaL rectifier) >
long phase 3 > prolonged QT > torsades
HCM
• Myosin binding protein C gene and Beta
myosin heavy chain gene mutations
Scar from a previous MI increases risk for
developing an arrhythmia
Dilated cardiomyopathy
• Sarcomere structural gene mutations
Pathology (Path)
4
89
Acute pericarditis In contrast to angina, the chest
pain of pericarditis is sharp and
pleuritic and may be exacerbated
by swallowing or coughing. PIP
occurs b/w 2 and 4 days
following a transmural MI. PIP is
an inflammatory rxn to cardiac
muscle necrosis that occurs in the
adjacent pericardium.
Cardiovascular (CV)
Fibrinous pericarditis post MI
• 24 days after MI
• Sharp, pleuritic pain that is exacerbated
by swallowing (suggests posterior
pericardium involvement) and radiating to
neck (suggest inferior pericardium
involvement)
• Must have transmural necrosis
• Tx: aspirin
Dressler's
• 4• 10 weeks after MI
• Fever, pleuritis, leukocytosis, pericardial
friction rub, new pericardial or pleural
effusion
• Autoimmune attack against heart
• Tx: aspirin, NSAIDs or steroids
Pathology (Path)
5
91
Long QT
syndrome
92
Dilated
cardiomyopathy
94
Amyloidosis
95
Hypertrophic
cardiomyopathy
98
Constrictive
pericarditis
Jervell and Lange-Nielsen
syndrome is an AR disorder Chx
by profound bilateral
sensorineural hearing loss and
congenital LQTS, which
predisposes to ventricular
arrhythmias and SCD. This
condition occurs 2° to mutations
in genes that encode voltagegated K channels.
Cardiovascular (CV)
Pathology (Path)
4
Cardiovascular (CV)
Pathology (Path)
8
Cardiovascular (CV)
Isolated Atrial Amyloidosis
• ANP localized to atria only
Medullary carcinoma of thyroid
• Calcintonin in thyroid
Pituitary gland amyloid
• Prolactin derived proteins
Type 2 DM
• Amylin (islet amyloid protein)
Alzheimer
• Beta amyloid plaques
MM
• Ig light chains (especially lambda)
• Deposit in heart, skin, tongue, GI, kidney
and peripheral nerves
• Bence joint proteins in urine
Cardiovascular (CV)
HCM is caused by genetic
Hypertrophic Cardiomyopathy
mutations affecting structural
• AD with variable expression
proteins of the cardiac sarcomere • Haphazard hypertrophied myocytes
(eg, β-myosin heavy chain,
Viral myocarditis
myosin-binding protein C) and is • lymphocytic interstitial inflammatory
one of the most common causes infilitrate
of SCD in young adults.
Hypersensitivity myocarditis
Histologically, it is Chx by
• Interstitial inflammatory infiltrate or
cardiomyocyte hypertrophy w/
mononuclear inflammatory cells and
haphazard cellular arrangement eosinophils
and interstitial fibrosis.
Pathology (Path)
1
Pathology (Path)
9
Pathology (Path)
2
Congenital Prolonged QT
Jervell Lange Nielsen
• K channel issue
• Neurosensory deafness
• AR
Romano ward
• K channel issue
• No deafness
• AD
Brugada
• Na channel issue
• Asians
Syndactylyl
• Failed separate of digits
Hereditary Hemorrhagive Telangiectasia
(Osler Weber Rendu)
• AD
• Vascular telangiectasias
R
t bl d
Dilation of the LV cavity
Nonvalvular HF Ischemic and Dilated
commonly occurs in response to • Normal of decreased wall thickness
systolic dysfxn (eg, ischemic
• Increased ventricular cavity size
heart disease, DCM) or certain
• Decreased contractile function
types of valvular disease (ie, AR, • Normal diastolic function
MR). Chronic volume overload Hypertensive or hypertrophic
causes progressive eccentric
• HTN: globally increased wall thickness
hypertrophy that eventually leads • Hypertrophic: increased septal thickness
to ↓ ventricular contractility and • Decreased ventricular cavity size
DHF.
• Normal contractile function
• Decreased diastolic function
RCM can be caused by
infiltrative diseases (e.g.
amyloidosis, sarcoidosis,
hemochromatosis) and often
results in diastolic HF due to
ventricular hypertrophy w/
impaired ventricular filling.
Cardiac amyloidosis is
characterised histologically by
areas of myocardium infiltrated
by an amorphous and acellular
pink material (amyloid).
In constrictive pericarditis,
Cardiovascular (CV)
Constrictive pericarditis
normal pericardium is replaced by • Viral, surgery, radiation or TB
dense, rigid pericardial tissue that • JVD, kussmaul sign (rise in JVD with
restricts ventricular filling,
inspiration), pulsus paradoxus, pericardial
leading to low CO and progr right- knock
sided HF. PEx findings in such
• Pericardial knock: sharp more
pts incl ↑ JVP, pericardial knock, accentuate sound heard before S3 normally
pulsus paradoxus, and a
would be
paradoxical ↑ in JVP w/
Pulmonary HTN
inspiration (Kussmaul sign).
• Loud P2
176
Myocardial
infarction
Mitochondrial vacuolization is
typically a sign of irreversible cell
injury, signifying that the
involved mitochondria are
permanently unable to generate
ATP.
Cardiovascular (CV)
Irreversible Injury
• Mitochondrial vacuoles and phospholipid
containing amorphous densities
Reversible Injury
• Myofibril relaxation
• Disaggregation of polysomes
• Disaggregatiuon of granular and fibrillar
elements of the nucleus
• Nuclear chromatin clumping
• Triglyceride droplet accumulation
(especially in hepatocytes)
• Glycogen loss
Pathology (Path)
18
179
Coronary blood
flow
In 90% of individuals, occlusion
of the RCA can result in
transmural ischemia of the
inferior wall of the LV, producing
ST elevation in leads II, III, and
aVF as well as possible sinus
node dysfxn. Occlusion of the
proximal LAD would be expected
to result in anteroseptal
transmural ischemia, w/ ST
elevations in leads V1-V4.
Occlusion of the LCX would
produce transmural ischemia of
the lateral wall of the LV, w/ ST
elevations mainly in V5 and V6,
and possibly also in I and aVL.
Inferior wall MI
• aVF, 2 and 3 ST elevation
• RCA occlusion
• Bradycardia due to SA nodal art block
LAD occlusion
• Can cause 2nd or 3rd degree HB
Cardiovascular (CV)
Pathology (Path)
9
180
Aging
Normal morphological changes in
the aging heart incl a ↓ in LV
chamber apex-to-base dimension,
devel of a sigmoid-shaped
ventricular septum, myocardial
atrophy w/ ↑ collagen deposition,
and accumulation of cytoplasmic
lipofuscin pigment w/i
cardiomyocytes.
Cardiovascular (CV)
Normal aging of heart
• Decreased LV size (apex base) >
sigmoid shape
• Increased interstitial CT +/ amyloid
• Lipofuscin: cytoplasmic brownish
granules
Dilated cardiomyopathy
• Increase risk of mural thrombi
Chronic hemolytic anemia
• Can result in hemochromotosis of heart
HCM
• Septal wall hypertrophy
Chronic ischemic heart
• Diffuse subendocardial vacuolization and
fibrosis
Pathology (Path)
8
181
Primary
hypertension
Concentric hypertrophy is
characterised by uniform
thickening of the ventricular wall
and narrowing of the ventricular
cavity due to ↑ afterload (e.g.
chronic HTN, AS). Eccentric
hypertrophy is characterised by ↓
ventricular wall thickness w/ an
assoc ↑ in chamber size due to
volume overload.
Cardiovascular (CV)
LVH
• Concentric: wall thickness
• Uniform thickening without change
outer dimensions of the heart
• MCC: long standing HTN followed by
AS
• Eccentric: cavity size
• Due to fluid overload (CHF or AR)
ASD
• RA and RV eccentric dilation
MR
• Eccentric LVH
MS
• LA dilation, normal LV
Normal aging
• Decrease LV chamber size (shortening
apex to base causing sigmoid septum)
Pathology (Path)
14
185
Chronic heart
failure
Alveolar hemosiderin-laden
macrophages indicate alveolar
hemorrhage. They most
commonly result from chronic ↑
of pulm capillary hydrostatic
pressure in the setting of leftsided HF.
HF due to LV dysfunction
• Pulmonary edema > RBC into alveoli >
phagocytosed by macrophages which
convert Fe from Hb to hemosiderin (HF
cells > golden cytoplasmic granules that
stains blue with Prussian blue)
COPD and asthma
• Hyper reactive airway
Granulomas in lung
• TB, fungus, sarcoid, beryllium
Cardiovascular (CV)
Pathology (Path)
12
188
Atrioventricular
canal defect
A complete AV canal defect is
comprised of an ASD, a VSD,
and a common AV valve. It's the
most common congenital cardiac
anomaly a/w Down syndrome.
Complete atrioventricular canal septal Cardiovascular (CV)
defect
• MC cardiac defect in Down Syndrome
• ASD + VSD + single AV valve
• Left to right shunting, AV valve regurg,
excessive pulmonary blood flow, HF
• Will hear AV valve regurg (best at apex)
and increase pulmonary venous return (mid
diastolic rumble)
Tuberous Sclerosis
• Tuberin and harmartin mutations
• Cardiac rhabdomyomas in ventricles
• Angiofibromas
• CNS hamartomas
Pathology (Path)
1
192
Myocardial
infarction
VF is the most common mech of
SCD due to AMI. It results from
arrhythmogenic foci triggered by
electrical instability in the
ischemic myocardium.
Acute MI
• Sudden Cardiac Death: Vfib or Vtach
within 48hr of MI
• MCC of death within 2 days of MI
Wall rupture
• 3• 7 days after MI
Cardiogenic shock
• From massive LAD MI
Cardiovascular (CV)
Pathology (Path)
18
203
Ventricular septal VSD typically presents in the
defect
neonatal period after pulm
vascular resistance has declined.
The clinical Px depends on the
size of the defect, which ranges
from an aSSx holosystolic
murmur (small VSD) to HF (large
VSD).
Cardiovascular (CV)
VSD
• Loud blowing holosystolic murmur at
mid/lower left sternal border
• Usually takes 4• 10days to present
• Small: asymptomatic
• Large: HF, failure to thrive,
diaphoresis with feeding (no murmur) >
can lead to pulmonary HTN then RVH
then eisenmenger
Pulmonary stenosis: innocent murmur due
to hypoplasia of branch pulmonary arteries
• Low grade, mid systolic, high pitch
blow murmur
Pathology (Path)
2
228
Endocarditis
Microemboli from the valvular
vegetations of BE are the most
common cause of subungual
splinter hemorrhages. The
presence of these lesions
necessitates careful cardiac
auscultation to detect a possible
new-onset regurgitant murmur.
Splinter hemorrhage in nails > think
infective endocarditis FROM JANE
• Fever Roth spot Osler node Murmur
Janeway lesion Anemia
• Nailbed hemorrhage Emboli
Cardiovascular (CV)
Pathology (Path)
15
230
Endocarditis
MVP w/ MR is the most common
predisposing condition for native
valve IE in developed nations.
Rheumatic heart disease remains
a freq cause of IE in devel
nations.
Cardiovascular (CV)
MVP
• MC underlying valvular disease
predisposing to infectious endocarditis in
DEVELOPED countries
• Rheumatic HD is the MC underlying
cause in DEVELOPING countries
• Bicuspid aortic valve, VSD, PDA and
unrepaired TOF increase risk too
CAD
• Can cause ischemia of papillary muscle
leading to MR
Pathology (Path)
15
231
Endocarditis
NBTE (marantic endocarditis) is
a form of non-infectious
endocarditis characterised by
valvular deposition of sterile
platelet-rich thrombi. It likely
results from valvular dmg due to
inflammatory cytokines in the
setting of an underlying
hypercoagulable state, and it's
most commonly seen w/
advanced malignancy (esp.
mucinous AC) or SLE.
Nonbacterial Thrombotic Endocarditis Cardiovascular (CV)
(marantic)
• Platelet rich thrombi attached to mitral
valve leaflets
• Common with advanced malignancy
(associated with mucin producing cancer)
• Endothelial injury > platelet deposition
• Vegations consist of bland thrombus with
strands of fibrin, immune complexes and
mononuclear cells
• Easily dislodged and embolize
Systemic Sclerosis
• Cor pulmonale, pericardial dz,
myocardial fibrosis and conduction system
disease
Pathology (Path)
15
Cardiovascular (CV)
Rheumatic Fever
• Mitral regurg early then mitral stenosis
• Mitral stenosis: causes atrial dilation
resulting in a fib or atrial mural thrombus
• Will see fusion of the commisures of
the cusps
• Opening snap with mid diastolic murmur
Mitral valve calcification is usually around
the annulus, seen in women over 60, and
asymptomatic
Rheumatoid Arthritis
• Can cause pericarditis or myocarditis
Pathology (Path)
7
Cardiovascular (CV)
Ortner Syndrome
• MS > LA dilation > compresses L
recurrent laryngeal nerve (neurapraxia)
leading to hoarseness
Reccurent laryngeal nerve
• Innervates all laryngeal muscles except
cricothyroid
Other causes of hoarseness
• Laryngeal edema
• Vascular disease
• Laryngeal mucosal disease (epi
sloughing)
• Vocal cord polyps
Interstitial myocardial
Aschoff body: pathognomonic for ARF Cardiovascular (CV)
granulomas (Aschoff bodies) are • Anitschkow cells (caterpillar cells)
found in carditis due to acute RF, • Hypersensitivity myocarditis: causes for
which develops after an un-Tx
loops, thiazides, ampicillin, azithromycin)
GAS pharyngeal infection.
• Viral myocarditis: adenovirus, coxsackie
Aschoff bodies contain plump
b, parvovirus b19
macrophages w/ abundant
cytoplasm and central, slender
ribbons of chromatin
(Anitschkow, or caterpillar cells).
Pathology (Path)
7
Pathology (Path)
5
Cardiovascular (CV)
Rheumatic fever
• Can develop 1 8 months after sore throat
• Restlessness and purposeless jerking
movements (sydenham chorea)
• Delayed autoimmune rxn to basal
ganglia
Parkinson
• Only time you will see jerking
movements is with levodopa OD
Pathology (Path)
5
Cardiovascular (CV)
AS
• Syncope, angina, dyspnea, fatigue
• In exercise, vasodilation without
compensatory increased CO due to AS
causes hypotension
• Hard crescendo descrescendo systolic
murmur @ 2nd R intercostal
• Can lead to an S4
• MCC: progressive valve leaflet
thickening and calcification
• Biscupid valve will see AS in 50's or
60's
Rheumatic valve
• Fusion of commissures
HCM
• Basal interventricular septum hypertrophy
with subaortic obstruction
MVP
• Myxomatous degen
AR
• Infective endocard
Pathology (Path)
8
232
Mitral stenosis
Rheumatic MS is characterised by
diffuse fibrous thickening and
distortion of the MV leaflets
along w/ commissural fusion at
the leaflet edges. Pts often present
w/ a diastolic murmur, dyspnoea,
and fatigue and are at ↑ risk of AF
and TE (e.g. stroke).
236
Mitral stenosis
LA enlargement can sometimes
cause left recurrent laryngeal
nerve impingement. Neurapraxia
resulting in left vocal cord paresis
and hoarseness may result.
240
Rheumatic fever
241
Rheumatic fever
Sydenham chorea presents w/
involuntary, rapid, irregular
jerking movements involving the
face, arms, and legs. It occurs
mos after group A streptococcal
infection and is one of the major
clinical MFx of acute RF. Pts w/
this condition carry a high risk of
chronic valvular disease.
242
Aortic stenosis
Calcific degeneration of the
trileaflet AV is the most common
cause of AS in developed nations.
AS is Chx by progressive AV
leaflet thickening and
calcification, leading to restricted
leaflet excursion and mobility.
AS murmur is usually a harsh
ejection-type systolic murmur
heard best at the base of the heart
in the "aortic area" (2nd right
ICS) w/ radiation to the carotid
arteries.
300
Aging
Lipofuscin is the product of lipid
peroxidation, accumulating in
aging cells (esp. in pts w/
malnutrition and cachexia).
Cardiovascular (CV)
Lipofuscin
• Yellow brown, finely granular
perinuclear pigment due to lipid
peroxidation
• Commonly seen in heart and live of aging
or cachectic, malnourish pt
Hemosiderin
• Fe overload
Melanin
• Oxidation product of tyrosine metabolism
Glycogen
• Clear vaculoes in cytoplasm
Hyaline
• Protein accumulation that is a glassy,
homogeneous pink
Pathology (Path)
8
442
Atherosclerosis
Atherosclerosis is initiated by
repetitive endothelial cell injury,
which leads to a chronic
inflammatory state in the
underlying intima of large elastic
arteries as well as in large- and
medium-sized muscular arteries.
Cardiovascular (CV)
Atherosclerosis
• Endothelial injry (HTN, hyperlipidemia,
smoking, diabetes, homocytseine, alcohol,
virus) > subendo collagen exposed >
monocytes adhere and platelets stick >
monocytes stimulate medial smooth muscle
migration and proliferation > foam cells
accumulate > chronic inflammation
continues to attract foam cells > SM form
fibrous cap
Pericytes are pluripotent cells in
postcapillary venules
Pathology (Path)
8
443
Coronary artery
disease
VSMCs are the only cells w/i the
atherosclerotic plaque capable of
synthesizing structurally
important collagen isoforms and
other matrix components.
Progressive enlargement of the
plaque results in remodeling of
the ECM and VSMC death,
promoting development of
vulnerable plaques w/ an ↑
propensity for rupture.
Cardiovascular (CV)
Atherosclerosis
• Endothelial damage increases expression
of surface vascular celL adhesion
molecules allowing adhesion and migration
of monocytes into the intima. Macrophages
release PDGF, FGF, endothelin 1 and IL 1
causing migration/proliferation of
vascular smooth muscle cells within the
INTIMA. Smooth muscle cells synthesize
collagen, elastin and proteoglycans
forming the fibrous cap.
• Macrophages release MMP that
degrade the fibrous cap
increasing vulnerability to rupture
Pathology (Path)
4
444
Atherosclerosis
Fatty streaks are the earliest
lesions of atherosclerosis and can
be seen as early as the 2nd decade
of life. They appear as a
collection of lipid-laden
macrophages (foam cells) in the
intima that can eventually
progress to atherosclerotic
plaques.
Abdominal Aorta
• Fatty streak first appears in teens
Sequence
• Endothelial damage
• LDL accumulated within vessel wall
• Macrophages migration and become
foam cells
• Growth factor released by platelets,
macrophages and endothelial cells
• Smooth muscles migrate, proliferation
and form fibrous cap
Cardiovascular (CV)
Pathology (Path)
8
446
Atherosclerosis
During the development of
atherosclerotic plaque (atheroma),
activated macrophages, platelets,
and endothelial cells release GFs
(eg, PDGF) that stimulate
recruitment of SMCs from the
arterial wall media and their
subsequent proliferation in the
intima.
Atheroma
• Endothelial cell injury > altered gene
expression > platelet adhesion > platelets
release PDGF (also by dysfunction
endothelial cells and macrophages > SM
migration into intima > SM proliferation
• Platelets also release TGFbeta
Cardiovascular (CV)
Pathology (Path)
8
447
Atherosclerosis
The likelihood of plaque rupture
is related to plaque stability rather
than plaque size or the degree of
luminal narrowing. Plaque
stability largely depends on the
mech strength of the fibrous cap.
Inflammatory macrophages in the
intima may ↓ plaque stability by
secreting metalloproteinases,
which degrade ECM proteins
(e.g. collagen).
Cardiovascular (CV)
Athero
• Symptoms at 70% occlusion
• Plaque stability depends on fibrous cap
production (smooth muscle cells) vs the
breakdown of the cap by inflammation and
macrophages (that secrete
metalloproteinase)
• Thinner the cap, the easier the rupture
HMG CoA reductase: cholesterol synth
• Lysyl oxidase: covalently crosslinks
collagen
• Needs Cu
• High activity would increase cap
thickness and make more stable
Procollagen peptidase: cleaves terminal
ends (def in Ehler Danlos)
Pathology (Path)
8
448
Peripheral
vascular disease
Intermittent claudication
describes muscle pain that's
reproducibly caused by exercise
and relieved by rest; it occurs due
to atherosclerotic stenoses (lipidfilled intimal plaques) in the large
arteries that prevent sufficient
blood flow to exercising muscle.
The lower extremities are most
commonly affected; however,
proximal lesions (i.e. aortoiliac
occlusion) can cause gluteal
claudication a/o impotence.
Peripheral Artery Disease
• Claudication
• Lipid dille intimal plaques obstructing
arterial lumen
• Tx: cilostazol
Cardiovascular (CV)
Pathology (Path)
4
449
Primary
hypertension
HTE is severely ↑ BP (typically
>180/120 mm Hg) w/ evidence of
end-organ dmg. In the kidneys,
this can MFx as malignant
nephrosclerosis, Chx by fibrinoid
necrosis and hyperplastic
arteriolosclerosis ("onion-skin"
appearance). A MAHA can occur
due to erythrocyte fragmentation
and platelet consumption at the
narrowed arteriolar lumen.
Hyperplastic arteriolosclerosis
• Diastolic over 130
• Onion rings
• Renal art stenosis > HTN >
decreased blood to kideny > more RAAS
> vicious cycle
Accelerated malignant HTN
• Retinal hemorrhage, exudates or
papilledema
Cardiovascular (CV)
Pathology (Path)
14
451
Peripheral
vascular disease
Thromboangiitis obliterans
(Buerger disease) is a segmental,
inflammatory vasculitis that
affects the small- and mediumsized arteries and veins of the
distal extremities w/
inflammatory, intraluminal
thrombi and sparing of the vessel
wall. It is usually seen in young,
heavy smokers, and can Px w/
digital ischemia and ulceration,
extremity claudication, Raynaud
phenomenon, and superficial
thrombophlebitis.
Cardiovascular (CV)
Buerger's
• Immune HSN to component of tobacco
smoke or direct endothelial cell toxicity
from tobacco smoke
• Vascultiis of Radial and Tibial arteries
• Thrombosing vasculitis that extends into
contiguous veins and nerves
• Isreal, Japan and India ethnicity
Onion like concentric thicking
• Malignant HTN (Diastolic > 120)
Polyarteritis Nodosa
• Transmural inflammation of arterial wall
with fibrinoid necrosis
Pathology (Path)
4
452
Takayasu arteritis Takayasu arteritis is a chronic,
large-artery vasculitis that 1arily
involves the aorta and its
branches. It presents w/
constitutional (e.g. fever, weight
loss) and arterio-occlusive (e.g.
claudication, BP discrepancies,
pulse deficits) findings in pts age
<40. Histopathology shows
granulomatous inflammation of
the vascular media.
Cardiovascular (CV)
Pathology (Path)
1
Leukocytoclastic vasculitis
• Microscopic polyangitis, microscoping
polyarteritis, hypersensitivity vasculitis
(RA)
• Segmental fibrinoin necrosis of small
vessels
• Similar to PAN
Granulomatous inflammation of media
• Takayasu and Temporal arteritis
453
Renal artery
stenosis
RAS is most often due to
atherosclerosis. It can cause
severe, refractory HTN due to
activation of the RAAS. Over
time, renal atrophy may occur due
to chronic O2 and nutrient
deprivation. Histologic Ex may
show crowded glomeruli,
tubulointerstitial atrophy and
fibrosis, and focal inflammatory
infiltrates.
Renal Artery stenosis
• MCC: atheromatous plaque
• Eventual renal atrophy due to lack of
oxygen and nutrients
• Atrophich kidney: crowded glomeruli,
tubulointerstitial atrophy and fibrosis
Cardiovascular (CV)
Pathology (Path)
9
460
Polyarteritis
nodosa
PAN is segmental, transmural,
necrotizing inflammation of
medium- to small-sized arteries.
Renal artery involvement is often
prominent. Vessels of the
kidneys, heart, liver, and
gastrointestinal tract are most
commonly involved in resulting
ischemia, infarction, or
hemorrhage. Cutaneous
manifestations occur in up to onethird of patients, and include
palpable purpura. The lung is
very rarely involved.
Polyarteritis Nodosa
• Segmental, transmural, necrotizing
inflammation of medium size arteries
• Kidney, heart, liver and GI commonly
involved
• Spares the lung
• Bears on a string appearance
• Can have palpable purpura or livedo
reticularis
Cardiovascular (CV)
Pathology (Path)
2
462
Aortic aneurysm
Myxomatous changes w/ pooling
of proteoglycans in the media
layer of large arteries are found in
CMD, which predisposes to the
devel of ADs and AAs. Medial
degen is freq seen in younger
individuals w/ Marfan syndrome.
Cardiovascular (CV)
Myxomatous changes found in Cystic
Medial Degeneration
• Fragmentation of elastic tissue and
separation of elastic and fibromuscular
components of tunic media, cleft like space
filled with amorphous extracellar matrix
• Seen in Marfans
• Lead to aortic aneurysms and
dissections
Beta aminopropionitrile (found in sweet
peas) inhibits lysyl oxidase and will mimic
Marfan syndrome
False aneurysm
• Leakage of blood causing hematoma
outside of vascular wall
Pathology (Path)
6
463
Aortic aneurysm
AAA is a/w RFs (e.g. age >60,
smoking, HTN, male sex, FHx)
that lead to chronic transmural
inflammation and ECM
degradation w/i the wall of the
aorta. This leads to weakening
and progr expansion of the aortic
wall, resulting in aneurysm
formation, typically below the
renal arteries.
Pathology (Path)
6
464
Aortic dissection
Cardiovascular (CV)
AAA
• Over 60
• Smoking
• HTN
• Male
Characterized by transmural inflammation
• > loss of elastin
• > abnormal collagen remodeling
Cystic medial necrosis: loss of smooth
muscle, collagen and elastic tissue (seen in
Marfans)
Vasa Vasorum Endarteritis (endarteritis
obliterans) is seen in thoracic AA
(infrarenal abdominal aorta lacks vasa
Cardiovascular (CV)
AD classically presents w/ severe Aortic Dissection
retrosternal pain that radiates to • Chest pain radiationg to the back
the back. This condition develops • Tears through aortic intima
when overwhelming
• Type A: any portion of ascending aorta
hemodynamic stress leads to
involved (can also involve descending)
tearing of the aortic intima w/
• Type B: only involved descending aorta
blood subseq dissecting thru the
• HTN is largest risk factor > vasa
aortic media. The resulting
vasorum occlusiong > decreased blood to
intramural hematoma can extend media > degenerates SM in media +
both proximally and distally and increased wall stiffness > tear
can compress major arterial
Aortitis
branches and impair blood flow. • Takayasu and giant cell arteritis
Aortic anuerysm
• Syphilis > obliterative endarteritis
Pathology (Path)
6
Cardiovascular (CV)
Pathology (Path)
6
Hereditary Hemorhagic Telangiectasia
(Osler Weber Rendu)
• Skin and mucosal telangiectasias
• Recurrent nosebleeds, GI bleeding and
hematuria
Sturge Weber
• Facial angiomas
• Leptomeningeal angiomas
• Mental retardation
• Seizures
• Hemiplegia
• Skull radiopacities
• Tram track calcifications
• Pheo
Tuberous Sclerosis
• Hamartomas in CNS and skin
• Angiofibroma
• Renal angiomyolipoma
• Cardia rhabodmyoma
• Seizure
Cardiovascular (CV)
Pathology (Path)
1
HTN is the single most important
RF for the devel of intimal tears
leading to AD. HTN, smoking,
DM, and hypercholaemia are all
major RFs for atherosclerosis,
which predisposes more to AA
formation than AD.
Aortic dissection
• "Septum" seen in aorta is tunica intima
• HTN is the most important risk factor
• Cystic medial degeneration in Marfans
predisposes to young aortic dissection
For Step 1
• Diabetes = CAD
Hypercholesterolemia
• Predisposes to aortic aneurysm
Smoking
• Thromboangiitis obliterans of radial and
tibial art
Syphilis
• Vasa vasorum obliterans > ascending
aortic aneurysm
Cardiovascular (CV)
Pathology (Path)
6
Varicose veins are dilated,
tortuous veins most commonly
found in the superficial veins of
the leg. They're caused by
chronically ↑ intraluminal
pressure a/o loss of tensile
strength in the vessel wall,
leading to incompetence to the
venous valves. Common
complications incl oedema, stasis
dermatitis, skin ulcerations, poor
wound healing, and infections.
Cardiovascular (CV)
Varicose veins Risk factors
• Prolonged standing, over 50, obesity,
multiple pregnancies Cause
• Incompetent valves Complication
• Painful thromboses, stasis dermatitis, skin
ulcerations (common over medial
malleolus), poor wound healing and
superficial infections
Random
Peripheal artery disease = claudication
Phlegmasia alba dolens: result of
iliofemoral venous thrombosis in
peripartum women
Pathology (Path)
3
466
Hemangioma
Cutaneous, strawberry-type
capillary hemangiomas are
common, benign, congenital
tumors, which are composed of
unencapsulated aggregates of
closely packed, thin-walled
capillaries. Initially, strawberry
hemangiomas grow in proportion
to the growth of the child, before
eventually regressing. In 75-95%
of cases, the vascular tumor will
regress completely by age 7.
469
Hereditary
hemorrhagic
telangiectasia
Osler-Weber-Rendu syndrome
(hereditary hemorrhagic
telangiectasia) is an AD condition
marked by the presence of
telangiectasias in the skin as well
as the mucous membranes of the
lips, oronasopharynx, resp tract,
GIT, and urinary tract. Rupture of
these telangiectasias may cause
epistaxis, GI bleeding, or
hematuria.
473
Aortic dissection
474
Chronic venous
insufficiency
475
Thrombophlebitis A PNPS of hypercoagulability
may be seen in some pts w/ ca,
especially ACs of the pancreas,
colon, or lung. Superficial venous
thromboses may therefore appear
in one site and then resolve, only
to recur in another site. This is
known as Trousseau syndrome
(migratory superficial
thrombophlebitis), an indication
of visceral ca.
Cardiovascular (CV)
Trousseau Syndrome
• Migratory thrombophlebitis
• Risk of visceral cancer (especially mucin
producing and pancreating)
Celiac
• Risk of hemorrhagic diathesis (vit k def)
Hyperthyroid
• Can cause hypercoag state
Pathology (Path)
1
506
Subdural
hematoma
SDH occurs due to the rupture of
cortical bridging veins. In young
pts, it results from a fall or MVA
and MFx w/ gradual onset of h/a
and confusion. In elderly pts it
may occur after a minor trauma
and present w/ a variety of neuro
SSx. You should know how to
recognise this on CT scan.
Cardiovascular (CV)
Subdural hematoma
• Rupture of bridging cortical veins
• Gradual onset of symptoms
• Crescent shaped mass that can cross
suture lines
• Elderly, shaken baby, and alcoholics
Epidural
• Middle meningeal art
• Biconvex mass
Lateral striate art
• Supply basal ganglia and internal capsule
Pathology (Path)
1
809
Renal infarction
Renal infarction presents w/ flank
pain, hematuria, ↑ LDH, and a
wedge-shaped kidney lesion on
CT scan. The most common
cause of renal infarction is
systemic TE, often due to
thrombus formation during AF.
The brain and kidneys are more
likely than other organs to suffer
embolic infarctions b/c they are
perfused at a higher rate.
Pathology (Path)
2
878
Chronic venous
insufficiency
Cardiovascular (CV)
Renal infarction
• Pale wedge shaped infarcts on CT, flank
pain, hematuria, elevated LDH
• MCC: thromboembolism (usually from
heart)
• Coagulative necrosis
Lower Leg DVT
• PE
• Stroke due to PFO
FSGS
• Loss of antithrombin 3 causes
hypercoaguable state
Acute Interstitial nephritis
• Fever, rash, eosinophilia/uria
Cardiovascular (CV)
Chronically ↑ venous pressure in Varicose veins
the ↓ extremities can lead to
• Caused by incompetent valves
incompetent venous valves and
• Can result in venous stasis dermatitis
venous dilation (varicose veins).
• Risk factors: obesity and pregnancy
Venous congestion and tissue
Lymphedema
ischemia can result in venous
• Obstruction of lympoid capillaries
stasis dermatitis.
• Marked swelling of dorsum of distal limb
• Initially soft and pitting but eventually
becomes firm and nonpitting > leads to
fibrosis of skin
Pathology (Path)
3
939
Aortic stenosis
Pathology (Path)
8
The murmur of valvular AS is
typically an ejection or
midsystolic murmur of crescendodecrescendo configuration w/
max intensity over the right 2nd
ICS and radiation to neck and
carotid arteries. The most
common cause of AS in elderly
pts (age >70) is degen
calcification of the AV leaflets.
Cardiovascular (CV)
AS or PS
• Crescendo descrescendo systolic murmur
peaking at midsystole radiating to carotids
• MCC: calcification
Ankylosing spondylitis
• Aortitis > AR
MR
• Chordal rupture
Thoracic aortic aneurysms and AR
• Cystic medial necrosis
Cardiovascular (CV)
MVP with MR
• Midsystolic click with late systolic murmr
best heard at the apex
• Disappears with squatting (increased VR
> leaflets don't snap as hard)
• Myxomatous degeneration (pathologic
degen of connective tissue)
• Seen in Marfans and Ehlers danlos
and OI
• Proliferation of spongiosa in leaflets,
fragmentation of elastin fibers with
increase mucopolysaccharides and type 3
collagen deposition
Pathology (Path)
1
Acute pericarditis Pericarditis is the most common
CV MFx a/w SLE. It presents w/
sharp pleuritic chest pain that is
relieved by sitting up and leaning
forward.
Cardiovascular (CV)
Acute pericarditis
• SLE
• Middle or left chest pain that radiates to
neck shoulder (trapezius ridge) > worsens
with inspiration and relieved by leaning
forward
• Can hear pericardial friction rub
Aortic dissection
• Long standing HTN, Marfan and Ehlers
danlos
Cardiac tamponade
• Beck's triad: Hypotension, distant heart
sounds and JVD
• Also pulsus paradoxus
Non bacterial endocarditis (Libman Sacks)
• Both sides of valves
Pathology (Path)
5
1439
Cardiac
tamponade
Cardiovascular (CV)
Cardiac Tamponade
• Pulsus parasoxus
• Beck's: JVD, hypotension and muffled
heart sounds
• Tachycardia
Tension pneumothorax
• Hypotension
• Tachycarida
• Tachypnea
• JVD
• Absent breath sounds and hyperresonance
Epidural hematoma
• Cushing's triad: HTN, bradycardia,
decreased RR
Pathology (Path)
2
1852
Kawasaki disease Kawasaki disease is a vasculitis
of medium-sized arteries that
presents w/ persistent fever for
>5days, bilateral conjunctivitis,
cervical LAD, and
mucocutaneous involvement.
Coronary artery aneurysms are a
serious complication of Kawasaki
disease.
Pathology (Path)
1
1882
Myocardial
infarction
Cardiovascular (CV)
Kawasaki
• Asian children under 5
• Fever for 5 or more day
• Bilateral non exudative conjunctival
injection
• Cervical lymphadenopathy
• Erythema of palatine mucosa, fissure
erythematous lip and strawberry tongue
• Edema of hands and feet, erythema of
palms and soles, desquamation of the
fingertips
• Rash on extremities that spreads
centripetally to trunk
• Development of coronary artery
aneurysm
Marfan or HTN
• Dissecting aneurysm
Temporal arteritis
M
l bli d
Cardiovascular (CV)
Ion pump failure due to ATP
Myocardial swelling due to ischemia
defic during cardiac ischemia
• Low ATP > low Na/K pump and Ca
causes intracellular accumulation SERCA pump > high Na and Ca inside
of Na+ and Ca2+. The ↑
cell causes swelling (also in mitochondria)
intracellular solute conc draws
• Intracellular K will be low
free water into the cell, causing
the cellular and mitochondrial
swelling that's observed
histologically.
Pathology (Path)
18
947
Mitral valve
prolapse
1040
MVP is most often caused by
defects in connective tissue
proteins that predispose to
myxomatous degen of the mitral
leaflets and chordae tendineae.
Cardiac auscultation typically
reveals a MC f/b a MR murmur;
the click and murmur occur later
in systole or disappear completely
w/ manoeuvres (e.g. squatting)
that ↑ LV EDV.
The combo of JVD, hypotension,
and muffled heart sounds is
highly suggestive of cardiac
tamponade. Tachycardia and
pulsus paradoxus are also freq
seen w/ tamponade. Lung Ex is
normal, which can help
distinguish cardiac tamponade
from tension PTX.
Cardiovascular (CV)
Infective endocarditis
• Predisposed by RF, MVP, prosthetic
valves
RF
• Mitral valve inflammation and scarring
Myocardial hypertrophy
• HTN, AS and HCM
Myocardial fibrosis
• Sarcoid, amyloid, Chagas, myocarditis,
prior MI
Vegetations are caused by
Cardiovascular (CV)
Infective Endocarditis
bacterial colonization and growth • Initially due to disruption of normal
on a sterile fibrin-platelet nidus
endocardial surface
that forms on the
• Typical atrial surface of AV valve or
damaged/disrupted endothelial
ventricular surface of semilunar valve
surface of the valvular apparatus.
• Fibrin and platelets allow for
adherance
Endomyocardial fibrosis: restrictive
cardiomyopathy
characterized by thickening and fibrosis of
apical endocardial surface (tropical
regions)
Myxomatous degeneration of mitral valve:
thickened and redundant mitral leaflet with
elongated chordae > prolapse
Pathology (Path)
15
Pathology (Path)
15
In unilateral RAS, the narrowed
renal artery causes hypoperfusion
of the affected kidney w/ subseq
ischemic dmg (e.g. tubular
atrophy, interstitial ischemia,
glomerular crowding). In
contrast, the contralateral kidney
is exposed to high BP and
typically shows changes of HTN
nephrosclerosis (e.g. arteriolar
wall thickening due to hyaline or
hyperplastic arteriolosclerosis).
Cardiovascular (CV)
Pathology (Path)
9
7616
Acute heart failure Acute cardiogenic pulm oedema
results from ↑ pulm venous
pressure. The alveolar capillaries
become engorged w/ blood and
there's a transudation of fluid
plasma across the alveolarcapillary membrane, appearing as
pink, acellular material w/i the
alveoli.
Cardiovascular (CV)
Pathology (Path)
7
7666
Myocardial
infarction
RV infarction (right-sided HF)
can lead to shock via impaired
forward blood flow to the left
heart, which ↓ left-sided preload
(↓ PCWP) and ↓ CO. The ↓ RV
output also ↑ RA and CVP.
Cardiovascular (CV)
Pathology (Path)
18
7667
Myocardial
infarction
Severe systemic hypotension (eg,
shock) is most likely to cause
ischemia 1st in areas of high
metabolic demand (eg,
hippocampus) or watershed
zones, which are areas that are
supplied by the distal branches of
two different major arteries.
Commonly affected areas in the
colon include the splenic flexure
and RSJ.
Cardiovascular (CV)
Pathology (Path)
18
2074
Endocarditis
2075
Endocarditis
7568
Renal artery
stenosis
Chronic valvular inflammation
and scarring a/w RHD predispose
to an ↑ risk of IE, which is Chx
by valvular vegetations w/
destruction of the underlying
cardiac tissue.
8296
Atrial myxoma
Myxomas are the most common
1° cardiac neoplasm and usually
arise w/i the LA. The tumours
typically cause positiondependent obstr of the MV,
leading to a mid-diastolic murmur
and SSx of ↓ CO (e.g. dyspnoea,
syncope). Constitutional SSx (e.g.
fever, weight loss) may also be
present. Histologically, the
tumours demonstrate scattered
cells w/i a mucopolysaccharide
stroma and abn blood vessels w/
hemorrhaging.
Cardiovascular (CV)
Cardiac myxoma
• Mid diastolic rumbling murmur best
heard at apex
• Positional cardiovascular symptoms
• Mucopolysaccharide stroma, abnormal
blood vessels, and hemorrhaging
• Produce IL 6 causing constitutional
symptoms
Acute Myeloid Leukemia
• Can met to the heart
• Will see pancytopenia, weakness, fatigue,
ecchymoses
Pathology (Path)
3
8458
Electrical injury
Although lightning injuries are
rare, they are a/w a 25% fatality
rate. Two-3rds of lightningrelated deaths occur w/i the 1st hr
after injury, w/ fatal arrhythmias
and resp failure as the most
common causes. Pts w/ minor
cutaneous involvement may still
have major internal injury after
lightning strikes and high-voltage
electrical contact.
Cardiovascular (CV)
Lightning related complications
Cardiac: arrhythmia
• Neuro: seizure, peripheral nerve damage,
respiratory failure Derm: lichtenberg
figures (fern lead pattern) and superficial
burns
• MSK: rhabdomyolysis, bone fx,
compartment syndrome Other: cataracts
(late), ruptured tympanic membrane,
curling
ulcer
Pathology (Path)
1
8610
Acute heart failure The CXR in ADHF typically
shows prominent pulm vessels;
patchy, bilateral airspace
opacification; and blunting of the
costophrenic angles due to pleural
effusions.
Sudden onset of SOB with orthopnea,
pulmonary edema, dilated heart > this
Acute Decompensated HF
• Kerley B line: short horizontal lines
situated perpendicularly to the pleural
surface that represent edema of the
interlobular
septa
Idiopathic Interstitiual Fibrosis: reticular
opacities and decreased long volume.
Present with progressive dyspnea and
nonproductive cough.
• COPD: flattened diaphragm
Pulmonary HTN: look for RVH and
enlarged pulmonary arteries
Cardiovascular (CV)
Pathology (Path)
7
11636
Atherosclerosis
Atherosclerosis is a PPx process
involving endothelial cell dysfxn,
and it develops most rapidly in
areas w/ bends and branch points
that encourage turbulent blood
flow. The lower abdo aorta and
coronary arteries are the vascular
beds most susceptible to
atherosclerosis; they tend to
develop atherosclerosis earliest in
life and have the highest overall
atherosclerotic burden.
Athero
• Abdominal aorta
• Coronary artery
• Politeal artery
• Carotid artery
• Diabetes = coronary artery athero
Cardiovascular (CV)
Pathology (Path)
8
11640
Costochondritis
Costosternal syndrome
(costochondritis) usually occurs
after repetitive activity and is
characterised by pain that is
reproducible w/ palpation and
worsened w/ movement or
changes in position.
Costosternal syndrome (costochonditis) Cardiovascular (CV)
• Pain is reproducable with palpation and
worsens with movement
Pleural or pericardial pain
• Worsens with inspiration
Aortic dissection
• Usually a difference of > 10 in each arm
Pathology (Path)
1
14789
Myocarditis
Acute myocarditis is most
commonly caused by a viral
infection (e.g. coxsackievirus,
adenovirus, influenza). It often
resolves w/o noticeable SSx, but
pts can develop serious
complications, incl
decompensated HF due to DCM
or SCD due to ventricular
arrhythmia. Histopathology
typically demonstrates
myofibrillary necrosis w/
inflammatory mononuclear
infiltrate.
Cardiovascular (CV)
Pathology (Path)
1
14964
Aortic stenosis
Cardiovascular (CV)
Pathology (Path)
8
14978
Myocardial
infarction
AS most commonly results from
age-related CAVD. The early
pathogenesis of CAVD closely
mimics that of arterial
atherosclerosis. In the later
stages, fibroblasts diffiate into
osteoblast-like cells and deposit
bone matrix, leading to progr
valvular calcification and
stenosis.
MI that causes ischemia of the
papillary muscle or nearby LV
wall can result in acute MR w/
development of a new systolic
murmur. Timely restoration of
blood flow can improve papillary
muscle dysfxn and lead to
resolution of the regurgitation.
Cardiovascular (CV)
Pathology (Path)
18
14980
Lymphedema
Chronic lymphedema is most
commonly caused by an acquired
disruption of lymphatic drainage
(eg, due to malignancy or
lymphadenectomy), and typically
presents with swelling and
thickened skin in one or more
extremities. Treatment is usually
conservative and involves
compression bandages and
physiotherapy; diuretics are
ineffective and contraindicated.
Cardiovascular (CV)
Pathology (Path)
1
14989
Stress
cardiomyopathy
Stress-induced (takotsubo)
cardiomyopathy is characterised
by hypokinesis of the mid and
apical segments and hyperkinesis
of the basal segments of the LV,
resulting in systolic dysfxn. The
condition is likely caused by a
surge of catecholamines in the
setting of physical or emotional
stress. It usually affects
postmenopausal women and
resolves on its own w/i several
wks.
Cardiovascular (CV)
Pathology (Path)
1
14992
Dilated
cardiomyopathy
Peripartum cardiomyopathy is a
relatively uncommon cause of
DCM that may be related to
impaired fxn of angiogenic GFs.
DCM involves compensatory
eccentric hypertrophy, which ↑
ventricular compliance and also
allows for temporary maintenance
of CO. Over time, ovewhelming
wall stress leads to LV failure w/
↓ EF and SSx HF.
Cardiovascular (CV)
Pathology (Path)
8
14993
Dilated
cardiomyopathy
DCM results from 1° myocardial
dysfxn leading to eccentric
remodelling of the LV. Pts can
develop LV mural thrombus and
are at risk for SCD due to
ventricular arrhythmia. Familial
DCM is typically inherited in an
AD pattern, and most commonly
results from truncating muts of
the TTN gene that codes for the
sarcomere protein titin.
Cardiovascular (CV)
Pathology (Path)
8
14997
Atrial myxoma
Myxomas are the most common
1° cardiac neoplasm and approx.
80% originate in the LA. Pts may
present w/ SSx MV obstr that
may worsen w/ certain body
positions, constitutional findings
(e.g. fever, weight loss), or
systemic embolisation (e.g.
stroke, mesenteric ischemia, acute
limb ischemia).
Cardiovascular (CV)
Pathology (Path)
3
14998
Atrial myxoma
Myxomas are the most common
1° cardiac neoplasm, and approx.
80% originate in the LA. Pts may
have systemic embolisation (e.g.
stroke) or SSx MV obstr that may
be worse w/ certain body
positions. Histopathologic Ex
reveals amorphous ECM w/
scattered stellate or globular
myxoma cells w/i abundant
mucopolysaccharide ground
substance.
Cardiovascular (CV)
Pathology (Path)
3
14999
Acute pericarditis Fibrinous pericarditis is the most
common type of pericarditis and
is Chx by pericardial
inflammation w/ a serous, fibrincontaining exudate in the
pericardial space. Pleuritic chest
pain and a triphasic friction rub
are frequently seen. Common
causes include viral infection, MI,
uremia, and rheumatologic
disease (eg, SLE, RA).
Cardiovascular (CV)
Pathology (Path)
5
15000
Acute pericarditis Viral infection is thought to be
the most common cause of acute
pericarditis. It causes a fibrinous
or serofibrinous pericarditis that
is often Chx by pleuritic chest
pain, a friction rub on cardiac
auscultation, diffuse ST elevation
on ECG, and mild to moderatesized pericardial effusion.
Cardiovascular (CV)
Pathology (Path)
5
15195
Aortic
regurgitation
Cardiovascular (CV)
Pathology (Path)
8
Eccentric ventricular hypertrophy
results in a dilated cavity w/
relatively thin ventricular walls
due to the addition of myocardial
contractile fibers in series in
response to chronic volume
overload. Chronic AR can result
from aortic root dilation and is a
common cause of eccentric
hypertrophy.
15196
Aortic stenosis
Concentric LVH involves
thickening of the ventricular
walls and ↓ in the ventricular
cavity size. It occurs via the
addition of myocardial contractile
fibers in parallel in response to
chronic pressure overload. AS
and prolonged systemic HTN are
common causes of concentric
LVH.
Cardiovascular (CV)
Pathology (Path)
8
15198
Pulmonary
stenosis
PV stenosis causes a crescendodecrescendo systolic murmur
(best heard at the left upper
sternal border) and delays closure
of the PV, resulting in widened
splitting of S2. Inspiration ↑
blood flow to the right side of the
heart, causing ↑ intensity of the
murmur and even later closure of
the PV.
Cardiovascular (CV)
Pathology (Path)
1
15542
Primary
hypertension
Concentric LVH involves
uniform thickening of the LV
walls w/ ↓ in LV cavity size and
most commonly results from
prolonged systemic HTN. It can
progress to HTN heart disease w/
impaired diastolic filling and HF
w/ preserved EF. Histopathology
demonstrates transverse
thickening of cardiomyocytes w/
prominent hyperchromatic nuclei
and interstitial fibrosis.
Cardiovascular (CV)
Pathology (Path)
14
15554
Pulmonary
embolism
Transcatheter aortic valve
implantation (TAVI) allows for
minimally invasive management
of severe aortic stenosis in elderly
patients who are unable to
tolerate open surgical valve
replacement. Paravalvular aortic
regurgitation is a common
complication of TAVI, resulting
from improper sealing of the
prosthetic valve to the native
aortic valve annulus.
Cardiovascular (CV)
Pathology (Path)
13
15555
Heart block
3rd-degree (complete) AV block
involves dysfxn of the AV node,
resulting in total lack of
communication b/w the atria and
ventricles. On ECG, there's
dissociation of P waves and QRS
complexes, w/ P waves marching
out at the intrinsic rate of the SA
node and QRS complexes at the
intrinsic rate of the His bundle or
ventricles (escape rhythm).
Cardiovascular (CV)
Pathology (Path)
2
15559
Lyme disease
Early disseminated Lyme disease
can have cardiac involvement
(Lyme carditis) that most
commonly MFx w/ varying
degrees of AV conduction block.
Pts may be aSSx, but those w/
complete AV conduction block
are likely to have dyspnea,
lightheadedness, or syncope.
Cardiovascular (CV)
Pathology (Path)
3
15839
Aortic aneurysm
TAAs are usually aSSx until they
grow large enough to compress
surrounding structures or cause
rupture. The most common SSx
presentation is chest or back pain,
but compression of nearby
structures can cause dysphagia,
hoarseness, cough, or dyspnoea.
Cardiovascular (CV)
Pathology (Path)
6
15840
Aortic aneurysm
Ruptured AAA is a Sx emergency
that usually Px w/ the acute onset
of severe abdominal and back
pain in pts w/ appropriate RFx
(eg, advanced age, smoking,
atherosclerosis). Accompanying
syncope, hypotension, and shock
may occur quickly
(intraperitoneal rupture) or may
be delayed (retroperitoneal
rupture).
Cardiovascular (CV)
Pathology (Path)
6
15885
Aortic dissection
The most common SSx of acute
AD is sudden onset of severe,
sharp or tearing chest and back
pain. Complications include
stroke, AR, and myocardial
ischemia. In addition, a dissection
can extend into the pericardium,
resulting in tamponade w/ ↓ CO
and shock.
Cardiovascular (CV)
Pathology (Path)
6
15886
Aortic dissection
Marfan syndrome involves a
deleterious mut in fibrillin that
mainly affects the structural
integrity of the CV and MSK
systems. Aortic root disease
predisposes to AD, which can
present w/ sudden-onset chest or
back pain, acute AR, and HF.
Common histologic findings in
aortic disease incl fragmentation
and loss of the elastic lamellae w/
fibrosis and CMD.
Cardiovascular (CV)
Pathology (Path)
6
15891
Aortic dissection
CMD (necrosis) is the classic
histologic finding in AD, as it
weakens the aortic wall and
allows a small intimal tear to
readily propagate. Collagen,
elastin, and smooth muscle are
replaced by a basophilic mucoid
ECM w/ elastic tissue
fragmentation and cystic
collections of
mucopolysaccharide.
Cardiovascular (CV)
Pathology (Path)
6
33
Bicuspid aortic
valve
AS is the most common
complication of bicuspid AVs.
Pts w/ bicuspid AVs develop
clinically significant AS on
average around age 50. In
comparison, senile calcific
stenosis of normal AVs generally
becomes SSx age >65.
Cardiovascular (CV)
Pathophysiology
(Patp)
1
Bicuspid aortic valve
• Shape causes increased hemodynamic
stress causing premature atherosclerosis
and calcification by mid 50's
(symptomatic)
• Less than 1% increased risk of aortic
dissection
• 23% increased risk for infective
endocarditis
• MCC of vfib in pt under 30 is
hypertrophic cardiomyopathy
42
Myocardial
infarction
Loss of cardiomyocyte
contractility occurs w/i 60 2nds
after the onset of total ischemia.
When ischemia lasts less than 30
min, restoration of blood flow
leads to reversible contractile
dysfxn (myocardial stunning), w/
contractility gradually returning
to normal over the next several
hrs to days. However, after about
30 min of total ischemia,
ischemic injury becomes
irreversible.
Cardiovascular (CV)
Total myocardial ischemia
• Heart will stop beating in 60 seconds
• Although there is still ATP around, ATP
in locations of high metabolic demand is
rapidly depleted and causes heart to stop
Ischemia less than 30 min > reversible
damage
• Myocardial stunning: prolonged
dysfunction of myocardium, function
returns within days
Adenosine is potent vasodilator in coronary
arteries (persistent ischemia depletes
adenosine
Pathophysiology
(Patp)
18
75
Dilated
cardiomyopathy
DCM results from direct dmg to
cardiomyocytes leading to
myocardial contractile dysfxn
(systolic dysfxn), volume
overload, and ventricular dilation.
Viral myocarditis is a common
cause of DCM and should be
suspected in young pts who
develop HF following a SSx viral
prodrome.
Cardiovascular (CV)
Decompensated HF
• Systemic and Pulmonary edema
• This viral origin in young pt with previos
URI like symtpoms
• Direct viral injury and autoimmune
rxn > inflammation > dialtion and systolic
dysfunction
• Also familial, alcohol, cocaine,
pregnancy, hemochromatosis
HTN
• Concentric LVH
AS
• High systolic pressure gradient across
aortic valve
MI
• Regional wall motion abnormality
HCM
• Asymmetric septal hypertrophy and
systolic anterior motion of mitral valce
Pathophysiology
(Patp)
8
85
Hypertrophic
cardiomyopathy
HCM is characterised by
asymmetric ventricular septal
hypertrophy and dynamic LVOT
obstr. ↓ in LV blood volume, via
manoeuvres or conditions that ↓
preload (e.g. abrupt standing,
Valsalva strain phase) or
afterload, worsen LVOT obstr
and ↑ the intensity of the HCM
murmur.
Cardiovascular (CV)
HOCM
• Harsh crescendo decrescendo systoil
murmur at lower left sternal border
• Decreased preload or decreased
afterload increase obstruction and murmur
> standing up would make murmur louder
• Increaed preload or afterload will
make murmur quieter >
squatting
Pathophysiology
(Patp)
9
90
Wolff-Parkinson- Wolff-Parkinson-White syndrome
White syndrome is characterized by symptomatic
paroxysmal supraventricular
tachycardia (eg, atrioventricular
reentrant tachycardia) due to the
presence of an accessory
conduction pathway. During
normal sinus rhythm, the presence
of this accessory pathway causes
ventricular preexcitation, which
can be identified on ECG by the
triad of a shortened PR interval,
early upslope of the QRS
complex (delta Wave), and a
widened QRS interval.
WPW triad
• Shortened PR interval (under 0.12)
• Wide QRS
• Delta wave
Cardiovascular (CV)
Pathophysiology
(Patp)
2
93
Restrictive
cardiomyopathy
Decompensated CHF
• Orthopnea, bibasilar crackles, JVD,
edema
Restrictive cardiomyopathy
• Reduced LV compliance
• Idiopathic, amyloidosis, sarcoidosis,
hemochromatosis
• Transthyretin: carrier of thyroxine >
mutation in TTR gene cause misfolding
and amyloid in the heart
Dilated CM
• Alcohol, doxorubicin, selenium, viral
myocarditis
• Increased LV compliance
Cardiovascular (CV)
Pathophysiology
(Patp)
1
Diastolic HF is caused by ↓
ventricular compliance and is
characterised by normal LV EF,
normal LV EDV, and ↑ LV filling
pressures. HTN, obesity, and
infiltrative disorders (e.g.
transthyretin-related amyloidosis,
sarcoidosis) are important causes
of DHF.
96
Cardiac
tamponade
CT typically presents w/
hypotension w/ PP, ↑ JVP, and
muffled heart sounds (HS; Beck's
triad). PP refers to an abn
exaggerated ↓ in SBP >10mmHg
on inspiration, and is a common
finding in pts w/ pericardial
effusion w/ CT.
Cardiovascular (CV)
Cardiac Tamponase
• Maliginancy, radiation
• Infection
• Hydralazing, isoniazid
• CT diseases
• Beck triad: hypotension, JVD and
muffled heart sounds
• Pulsus paradoxus
• Enlarged water bottle shaped heart
Constrictive pericarditis
• Takes months to develop
• Usually after radiation
Viral myocarditis
• Pulsus alternans: pulse amplitude changes
Pathophysiology
(Patp)
2
97
Acute pericarditis Acute-onset, sharp, and pleuritic
chest pain that ↓ w/ leaning
forward is char of acute
pericarditis.
Fibrinous/serofibrinous
pericarditis is the most common
form of pericarditis and a
pericardial friction rub is the most
specific physical finding. Viral
pericarditis is often preceded by a
URI.
Cardiovascular (CV)
Acute Pericarditis
• Sharp, pleuritic chest pain that decreases
when leaning forward
• High pitched, leathery and scratch
friction rub
• Commonly caused by MI, RF or uremia
• Viral fibrinous exudate can occur
Kussmaul Sign
• Increased JVD with inspiration
• Constrictive pericarditis, restrictive
cardiomyopathy, right HF, tricupsid
stenosis and rarely cardiac tamponase
Pulsus Paradoxus
• Cor pulmonale, constrictive pericarditis,
cardiac tamponade, COPD and asthma
Pathophysiology
(Patp)
5
186
Diastolic
dysfunction
Diastolic HF
• Normal EF
• Normal end diastolic volume
• Increased LV filling pressure
• Decreaed LV compliance
Systolic HF
• Decreased EF
• Increaed end diastolic volume
Cardiovascular (CV)
Pathophysiology
(Patp)
4
187
Congenital cardiac Increased blood oxygen
defects
saturation between 2 right-sided
vessels or chambers indicates the
presence of a left-to-right shunt.
If the abnormal oxygen increase
occurs between the right atrium
and the right ventricle, a
ventricular septal defect (VSD) is
likely present. Small VSDs
produce a holosystolic murmur
that is loudest over the lower left
sternal border.
Cardiovascular (CV)
VSD: loud holosystolic murmur best
heard over the left sternal border
• Increased RA and RV SpO2 but RV >
RA SpO2
• ASD: fixed S2 splitting
• SpO2 of RA and RV would be
identical
Bifid carotid pulse with brisk upstroke
indicated HOCM
Pathophysiology
(Patp)
2
189
Embolic stroke
Paradoxical emboli
• DVT through PFO, VSD, ASD or
pulmonary arteriovenous malformation to
brain
• ASD: wide and fixed splitting of S2
Random AR
• Early diastolic decrescendo murmur
HCM
• Systolic mumur that gets quieter with
standing MS or TS
• Diastolic murmur with presystolic
accentuation due to atrial contraction
• A fib causes murmur to disappear TS
or RBBB
• Wide split S1 that is accentuated by
inspiration
Cardiovascular (CV)
Pathophysiology
(Patp)
1
HF w/ preserved EF is Chx by
diastolic dysfunctlon, which
frequently occurs in the setting of
prolonged systemic HTN due to
concentric LVH. Pts w/
longstanding HTN have ↑ SVR.
Paradoxical embolism occurs
when a thrombus from the venous
system crosses into the arterial
circulation via an abnormal
connection b/w the right and left
cardiac chambers (eg, PFO, ASD,
or VSD). Atrial left-to-right
shunts cause wide and fixed
splitting of S2 and can facilitate
paradoxical embolism due to
periods of transient shunt reversal
(eg, during straining or
coughing).
Cardiovascular (CV)
Post MI
• Witin 24hr: Fibrinolytic therapy causing
intracranial or GI bleeding
• First 48/72hr: V fib then V tach
• Days 5 14: wall/septum/papillary rupture
Pathophysiology
(Patp)
18
Marfan syndrome CV lesions are the most lifethreatening complications a/w
MFS. Early-onset CMD of the
aorta predisposes to AD, the most
common COD in these pts.
Pathophysiology
(Patp)
2
195
Myocardial
infarction
Cardiovascular (CV)
Marfan
• Fibrillin 1 on chromosome 15
• MVP and cystic medial degeneration of
aorta
• MCC of death: aortic dissection
• 2nd MCC of death: cardiac failure due to
MVP or aortic regurg
Homocystinuria
• Marfan habitus
• Increased risk for athero and thrombotic
events
Cardiovascular (CV)
Rupture of the LV free wall is a Post MI Issues
catastrophic mechanical
• 514 days: macrophage rupture structure
complication of anterior wall MI in order from most to least common (free
that usually occurs w/i the 1st 5- wall leading to tamponade, septum leading
14 days after MI. Rupture leads to to VSD, papillary muscle leads to regurg)
hemopericardium and CT,
• 1 month+: true aneurysm leades to mural
causing profound hypotension
thrombus, arrhythmias, HF or rarely
and shock w/ rapid progression to rupture
PEA and death.
Pathophysiology
(Patp)
18
196
Pulmonary arterial PAH should be suspected in
hypertension
young and otherwise healthy pts
w/ fatigue, progr dyspnoea,
atypical chest pain, or
unexplained syncope. Longstanding PAH leads to
hypertrophy a/o dilation of the
RV (cor pulmonale).
Cardiovascular (CV)
Pulmonary HTN
• RV hypertrophy (cor pulmonale)
• Progressive dyspnea
• Primary: mid aged females
• Characteristic intimal hyperplasia and
fibrosis, medial hypertrophy and plexiform
lesions
Random
AS and HTN
• LV hypertrophy
WPW
• Sudden cardiac death in young pt
• Delta wave
Pathophysiology
(Patp)
8
198
Pulmonary arterial Left-sided HF can cause 2° PAH
hypertension
via ↑ left-sided diastolic filling
pressures transmitting backward
to the pulm veins, resulting in
pulm venous congestion. Over
time, pulm arterial remodelling
(medial hypertrophy and intimal
thickening w/ fibrosis) can occur,
but not to the extent that occurs in
(1°) PAH.
Cardiovascular (CV)
LHF
• MCC: HTN
• High LV pressure > high LA pressure >
pulmonary venous congestion > damages
pulmonary endotheium > low NO and high
endothelin produced > high resistance >
pulmonary art SM proliferation (medial
hypertrophy) and intimal thickening and
fibrosis > plexiform lesions
Other causes of Pulmonary HTN
• COPD
• Hypoxia
• Congenital left to right shunt
• Pulmonary fibrosis
• Recurrent PE
Pathophysiology
(Patp)
8
200
Mitral
regurgitation
Cardiovascular (CV)
Functional MR
• Holosystolic murmur heard in CHF pt
when fluid overloaded that disappears once
treatment is initiated and fluid is decreased
Mitral Valve calcification
• Calcification of annulus in pt over 60
• Asymptomatic
Pathophysiology
(Patp)
6
193
Myocardial
infarction
194
LV free-wall rupture is an
uncommon but devastating mech
complication of transmural MI
that occurs w/i 5 days or up to
2wks following the event.
Rupture leads to cardiac
tamponade that causes
hypotension and shock w/ rapid
progr to cardiac arrest. Autopsy
typically reveals a slit-like tear at
the site of infarction in the LV
wall.
DHF is a common cause of 2°
(fxnal) MV regurgitation. ↑ LV
EDV causes dilation of the MV
annulus and restricted movement
of the chordae tendineae w/
subsequent regurgitation. Tx w/
diuretics and vasodilators can
improve HF-induced MR.
201
Cardiovascular (CV)
Atrial septal defect Wide, fixed splitting of the 2nd
ASD
heart sound is a Chx auscultatory • Wide fixed splitting S2
finding in pts w/ ASD. A
• Increased pressure on right side of the
hemodynamically significant
heart
ASD can produce chronic pulm • Needs to be fixed in order to prevent
HTN as a result of left-to-right
pulmonary artery change
intracardiac shunting.
• High pressure in pulmonary arteries >
Eisenmenger syndrome is the late- medial hyperthropy that can become severe
onset reversal of a left-to-right
enough its pressure is great than systemic >
shunt due to pulm vascular
right to left shunt (Eisenmenger)
sclerosis resulting from chronic • Changes in pulmonary arteries are
pulm HTN. Closure of the ASD irreversible
may be required to prevent
Eisenmenger syndrome
irreversible pulm vascular
• Will see cyanosis, polycythemia and
sclerosis and a permanent
clubbing
Eisenmenger syndrome.
Hypertrophy of RA and RV are reversible
Pathophysiology
(Patp)
2
204
Tetralogy of Fallot In pts w/ TOF, the degree of
RVOT obstr is the major
determinant of the degree of R-L
intracardiac shunting and
resulting cyanosis.
Cardiovascular (CV)
TOF
• Right ventricular outflow tract (RVOT)
obstruction is most important factor for
severity
• Increases Right >Left shunting of
blood through VSD
• Degree is RVOT can change > tet
spells
• Associated with DiGeorge, Down and
Pathophysiology
(Patp)
3
227
Aortic
regurgitation
AR causes a decrescendo
diastolic murmur w/ maximal
intensity occurring just after
closure of the AV, when the
pressure gradient b/w the aorta
and LV is the highest. The
pressure tracing for AR is Chx by
loss of the aortic dicrotic notch,
steep diastolic decline in aortic
pressure, and high-peaking
systolic pressures.
AR
• Wide PP
• High pitched blowing descrescendo
diastolic murmur beginning immedaitely
after A2
Cardiovascular (CV)
Pathophysiology
(Patp)
8
233
Mitral stenosis
The best and most reliable
auscultatory indicator of the
degree of MS is the A2-OS
interval. A shorter interval
indicates more severe stenosis.
Other auscultatory findings can
incl a diastolic rumbling murmur
w/ presystolic accentuation due to
LA contraction.
Cardiovascular (CV)
Mitral Stenosis
• Best indicator of intensity is length of
time between S2 (technically A2) and
Opening Snap
• The worse the stenosis, the higher the
residual pressure in the L atrium causes a
louder and earlier opening snap
• Can lead to pulmonary HTN and right
sided HF
• When MS becomes sever enough to
precipitate A Fib, presystolic accentuation
of the MS murmur disappears
Pathophysiology
(Patp)
7
234
Mitral stenosis
Isolated MS causes ↑ upstream
pressures in the LA and pulm
veins and arteries. LV EDP is
normal or ↓ due to obstr of blood
flow thru the stenotic valve. An ↑
LV EDP suggests addnal
downstream pathology (e.g. AV
disease, LV failure).
Mitral stenosis
• High P difference between LA and LV
• High LA P > a fib and mural thrombus
• High pulmonary P > pulmonary
edema/hemorrhage
• High RV P > tricuspid regurg, JVD and
peripheral edema
Rheumatic fever
• MR early then MS late
• AS (primarily) and some AR: both
increase LV diastolic P
• Cusp fusion (fish mouth)
Chronic pulmonary HTN (due to MS)
• Decrease pulmonary vessel compliance,
reactive hypertrophy and partial
obliteration of pulmonary capillaries
Cardiovascular (CV)
Pathophysiology
(Patp)
7
Cardiovascular (CV)
Pathophysiology
(Patp)
7
Cardiovascular (CV)
Chronic AR
• Complication of infective endocarditis
• Increased preload > increase SV
• Eccentric hypertrophy (sarcomeres added
in series)
• Maintained CO
• Decreased aortic pressure in diastole
(afterload) > wide PP
Acute AR
• Small LV cavity
• Increased LV end diastolic P >
pulmonary edema
• Declined CO
• Reflex tach
AS
• Concentric hypertrophy
Cardiovascular (CV)
Aortic regurg
• Head bobbing (hyperdynamic pulse with
wide PP)
LV Restriction
• Small SV
LV Dilation
• Small SV and low PP
Pathophysiology
(Patp)
8
Pathophysiology
(Patp)
8
Cardiovascular (CV)
AS
• Large difference in pressure between LV
and aortic pressure
• Crescendo decrescendo murmur (loudest
mid systole > large difference in pressure)
Pathophysiology
(Patp)
8
Cardiovascular (CV)
Severe aortic stenosis
• Pt with chronic AS and concentric LVH,
atrial contraction contributes significantly
to LV filling
• 10% of pt develop a fib >sudden decrease
in left ventricular
filling due to loss of atrial contraction >
acute pulmonary edema and hypotension
Pathophysiology
(Patp)
8
235
Mitral stenosis
Cardiac auscultation in pts w/ MS Presystolic accentuation
reveals a loud 1st heart sound, an • Increase in diatolic murmur with atrial
early diastolic OS after the 2nd
kick
heart sound, and a low-pitched
diastolic rumble best heard at the
cardiac apex. The OS is caused
by the sudden opening of the MV
leaflets when the LV pressure
falls below the LA pressure at the
beginning of diastole.
237
Aortic
regurgitation
In chronic AR, persistent LV
volume overload triggers
eccentric hypertrophy, which
causes a compensatory ↑ in SV to
maintain CO. This compensatory
mech allows for a relatively long
aSSx in most pts; however, LV
dysfxn eventually occurs, leading
to HF.
238
Aortic
regurgitation
Chronic aortic regurgitation (AR)
causes a reduction in diastolic
blood pressure and a
compensatory increase in left
ventricular stroke volume. These
changes create a high-amplitude,
rapid rise-rapid fall pulsation (ie,
widened pulse pressure) and the
other characteristic findings of
AR (eg, head bobbing. "pistolshot" femoral pulses).
243
Aortic stenosis
The murmur of AS is a systolic
ejection-type, crescendodecrescendo murmur that starts
after the 1st heart sound and
typically ends before the A2
component of the 2nd heart
sound. The intensity of the
murmur is proportional to the
magnitude of the LV to aorta
pressure gradient during systole.
244
Aortic stenosis
In pts w/ chronic AS and
concentric LVH, atrial
contraction contributes
significantly to LV filling. Loss
of atrial contraction due to AF
can ↓ LV preload and CO
sufficiently to cause systemic
hypotension. ↓ forward filling of
the LV can also result in backup
of blood in the LA and pulm
veins, leading to acute pulm
edema.
246
Diastolic
dysfunction
A low-freq, late diastolic sound
on cardiac auscultation that
immediately precedes S1 is most
often S4. An abn S4 can be heard
in pts w/ ↓ ventricular compliance
(e.g. HTN heart disease, AS,
HCM) due to a sudden rise in
EDP w/ atrial contraction.
Cardiovascular (CV)
Gallops
•S3
• Immediately after S2
• Rapid ventricular filling
• Turbulent blood flow due to high volume
• Normal in children, young adults and
pregnancy
• Abnormal: over 40, HF, restrictive
cardiomyopathy, high output states
S4 (best heard with bell in lat decub at
apex)
• Just before S1
• Atrial contraction forcing blood into stiff
ventricle (HTN, AS, HCM)
• Normal in healthy older adults
• Abnormal: younger adults, children,
ventricular hypertrophy, acute MI
Pathophysiology
(Patp)
4
293
Peripheral
vascular disease
Phenotypically mixing refers to
coinfection of a host cell by 2
viral strains, resulting in progeny
virions that contain nucleocapsid
proteins from 1 strain and the
unchanged parental genome of
the other strain. B/c there's no
change in underlying viral
genomes (no genetic exchange),
the next gen of virions revert to
their original, unmixed
phenotypes.
Cardiovascular (CV)
Reperfusion injury
• High ROS generation by parenchymal
cells, endothelial cells, and leukocytes
• Irreversible mitochondrial damage
• Inflammation that attracts neutrophils
causing additional injury
• Activation of complement causing cell
injury
Random
• Cellular swelling: reversible injury
• Glutathione peroxidase decreases ROS
• Mitochondrial vacuolization: irreversible
injury but not directly associated with
increased creatine kinase
Pathophysiology
(Patp)
4
296
Aging
Dystrophic calcification occurs in
dmgd or necrotic tissue in the
setting of normal Ca lvls;
metastatic calcification occurs in
normal tissue in the setting of
hypercalcemia.
Dystrophic calcification of aortic valve Cardiovascular (CV)
• Occurs with cell injury and death
(necrosis) with normal Ca levels
• Stains dark purple on H&E
Random
Amyloidosis: restrictive cardiomyopathy
Hypercalcemia: metastatic calcification of
normal tissue
(especially in alkaline environement of
kidneys, lungs, arteries
and gastric mucosa)
Pathophysiology
(Patp)
8
726
Rheumatic fever
Acute RF is a complication of
untreated group A streptococcal
pharyngitis. RHD is the most
common cause of acquired
valvular heart disease and CV
death in developing countries.
The incidence of acute RF and
RHD has been ↓ in industrialized
nations w/ prompt Tx of
streptococcal pharyngitis w/
penicillin.
Acute Rheumatic Fever
• Anti GAS Ab attach host cardiac and
neuronal tissue
• JONES
• Tx: penicillin (prevents RF)
• Empiric tx: decrease RF related heart
disease
• Penicillin does not prevent PSGN
Serum sickness
• Associated with Hep B and penicillin
Cardiovascular (CV)
Pathophysiology
(Patp)
5
751
Prostacyclins
Prostacyclin (prostaglandin I2) is
synthesized from prostaglandin
H2 by prostacyclin synthase in
vascular endothelial cells. Once
secreted, it inhibits platelet
aggregation and causes
vasodilation to oppose the fxns of
thromboxane A2 and help
maintain vascular homeostasis.
Cardiovascular (CV)
Prostacyclins (PGI2 from PGH2)
• Synthesized in endothelium
• Inhibits platelet aggregation and
adhesion, vasodilation, increased
permeability and stimulates leukocyte
chemotaxis (all oppose TXA2)
• Damaged endothelium decreased
PGI2 synthesis and TXA2 predominates >
occlusion
Serotonin
• Produced by platelets
• Vasodilation and increased premeability
Kallikrein
• Converts kininogen > bradykinin
Protein C
• Inactivated Factor 5a and 8a
Pathophysiology
(Patp)
1
843
Chronic heart
failure
↓ CO in HF triggers neuroendo
compensatory mechanisms to
maintain organ perfusion;
however, the compensatory
mechanisms are maladaptive over
the long term. ↑ sympathetic
output and activation of the
RAAS stimulate vasoconstriction
and volume retention,
compounding the hemodynamic
stress on an already failing heart
and creating a vicious cycle of
decompensation.
CHF
• Decreased Co > RAAS stimulated
(vasoconstriction, Na retention, high
aldosterone) and increased sympathetic
output
Cardiovascular (CV)
Pathophysiology
(Patp)
12
943
Mitral
regurgitation
In pts w/ MR, LV afterload is
determined by the balance of
resistance b/w forward flow
(aortic pressure) and regurgitant
flow (LA pressure). A ↓ in SVR ↑
the ratio of forward to regurgltant
blood flow and improves CO.
Pathophysiology
(Patp)
6
944
Mitral
regurgitation
Cardiovascular (CV)
Mitral regurg
• Forward SV: blood in aorta
• Backward SV: blood into LA
• Amount of backward SV is related to
afterload (decreased afterload will decrease
backward SV)
Decreased HR > higher EDLVV > worse
backward SV
• Same as increase preload (if MR is
volume dependent)
• Increase contractility will wrosen
backward SV
Cardiovascular (CV)
Pts w/ severe MR develop leftMR
sided volume overload w/ an S3 • The best indicator of MR severity is the
gallop due to the large volume of presence of an S3 gallop (larger amout of
regurgitant flow re-entering the regurg leads to S3)
ventricle during mid-diastole. The MPV
absence of an S3 gallop excludes • Mid systolic click with occur earlier in
severe chronic MR.
systole with decrease LV volume
Pathophysiology
(Patp)
6
945
Mitral
regurgitation
LV systole corresponds to the
time of passive filling of the LA
(atrial diastole). MR leads to
markedly ↑ LA pressure during
this period, creating the char early
and large V wave on LA pressure
tracing.
Cardiovascular (CV)
Mitral regurg
• Elevation of the V Wave pressure
Aortic regurg
• Elevated LV diastolic pressure and
decrease aortic diastolic pressure
Aortic stenosis
• Abnormal pressure gradient across aortic
valve (LV systolic pressure >> aortic
systolic pressure)
Pathophysiology
(Patp)
6
952
Coronary blood
flow
↑ in resting blood flow to
ischemic myocardium are
primarily mediated by locallyacting substances (eg, adenosine,
NO) that trigger coronary
arteriolar vasodilation. Rx
arteriolar vasodilators (eg,
adenosine, dipyridamole) mimic
the vasodilation that occurs w/
exercise and may cause
redistribution of blood flow from
ischemic to nonischemic areas of
myocardium, so-called coronary
steal.
Cardiovascular (CV)
Coronary steal disease
• Coronary arteries distal to atheroma are
maximally dilated
• With adenosine or dipyridamole
(vasodilators) are given it will actually
shunt blood away from the ischemic areas
• Theory behind pharm stress test
Epicardial vessels
• RCA, LCA, LAD, Left circ
Pathophysiology
(Patp)
9
1532
Chronic heart
failure
The ↓ CO in HF leads to ↓ renal
perfusion and conseq stim of the
RAAS in a maladaptive effort to
maintain effective BV. Inactive
AT-I is converted into active ATII by endothelial-bound ACE in
the lungs.
Cardiovascular (CV)
CHF
• Increase Renin from JG cells
• Angiotensin (made by liver) > ang 1
(renin) in sysemic circulation
• Ang 1 > ang 2 (angiotensin converting
enzyme) in the lung
• This means higher ang 2 than ang 1 in the
pulmonary vein
Pathophysiology
(Patp)
12
1578
Cor pulmonale
Peripheral edema results from the
accumulation of fluid in the
interstitial spaces. Factors that
promote edema include elevated
capillary hydrostatic pressure,
decreased plasma oncotic
pressure, sodium and water
retention, and impaired lymphatic
drainage. In chronic heart failure,
increased lymphatic drainage
initially offsets factors favoring
edema, whereas acute changes
(eg, venous thrombosis, heart
failure decompensation) are more
likely to produce edema.
Cardiovascular (CV)
Transudate causes
• Elevated capillary hydrostatic pressure
• Abnormal arteriolar dilation or
imparied venous return
• Decreased plasma oncotic pressure
• Nephrotic, liver dz, malnutrition
• Sodium and water retention
• Increase intravascular volume
(increased capillary hydrostatic P)
• Lymphatic obstruction
• Causes by filariasis, malignancies, and
surgery/radiation
Moderate transudate can be offset by
compensatory increase in lymph drainage
preventing edema
Pathophysiology
(Patp)
1
2070
Jugular venous
pulse
On JVP tracings, the 1st peak is
the a wave, which is generated by
atrial contraction. This is notably
absent in pts w/ AF.
Pathophysiology
(Patp)
1
2071
Constrictive
pericarditis
Calcification and thickening of
the pericardium are common
features of constrictive
pericarditis on CT. CFx include
slowly progressive dyspnea,
peripheral edema, and ascites.
Jugular Venous Tracing A: right atrial Cardiovascular (CV)
contraction
• C: right ventricular contraction X: right
atrial relaxation
• V: right atrial filling
• Y: Right atrial emptying
Cardiovascular (CV)
Constrictive Pericarditis
• Thickened and calcified pericardium
• Slowly progressive dyspnea, chronic
edema and ascites
• Rapid y descent
• Causes: radiation of chest, cardiac
surgery and TB
Aortic dissection
• Sudden chest pain radiating to the back
HCM
• Prominent a wave
• Thickened interventricular septum
Ischemic heart
• Looks for calcification of coronary art or
aorta
Pathophysiology
(Patp)
2
2096
Mitral
regurgitation
MR results in a blowing,
holosystolic murmur heard best
over the cardiac apex w/ radiation
to the axilla. RHD is a very
common cause of MR in
underdeveloped countries.
Rheumatic Fever
• MR for the first few decades > then MS
Ascending Aortic Aneurysm
• Aortic regurg
Cardiovascular (CV)
Pathophysiology
(Patp)
6
2099
Pulsus paradoxus
PP is defined by a ↓ in SBP of
>10 mm Hg w/ inspiration. It is
most commonly seen in pts w/ CT
but can also occur in severe
asthma, COPD, and constrictive
pericarditis.
Cardiovascular (CV)
Pulsus Paradoxus
• Inspiration > more preload > RV expands
into LV (normally LV can move in
pericardal space) > but if can't then lower
LVEDV > small SV
• See with cardiac tamponade, COPD,
asthma, constrictive pericarditis
AS
• Pulsus parvus et tardus
MR
• Bound pulses with brisk uptroke
(increase LV ejection volumes)
Pathophysiology
(Patp)
2
Cardiovascular (CV)
Asthma or COPD causing pulsus
paradoxus
• MCC of pulses paradoxus in absence
of pericardial disease
• Give B2 agonist > Gs > increased cAMP
Cromolyn
• Stabilized mast cells preventing
degranulation
Corticosteroids
• Prevent eosinophil degranulation
Pathophysiology
(Patp)
2
Cardiovascular (CV)
Aortic regurg
• Early descendo diastolic murmur
• Can present with palpitations, atypical
chest pain, left HF
• The duration of the murmur gives
insight into severity (holodiastolic is
severe)
HCM
• Mitral regurg (systolic murmur)
MVP
• Midsystolic click
A bicuspid AV is a common
Cardiovascular (CV)
AS
cause of AS in the United States. • Harsh, crescendo decrescendo systolic
The classic auscultatory finding murmur @ R sternal border that radiates to
in pts w/ AS is a harsh, crescendo- carotids
decrescendo systolic ejection
• Syncope, angina and dyspnea
murmur heard best in the right
• Under 60 > think bicuspid aortic valve or
2nd ICS w/ radiation to the
rheumatic heart disease
carotids.
• Over 60 > calcification due to wear and
tear
Marfans
• Aortic dilation > AR
• Aortic dissection
MVP
• Mid systolic click @ cardiac apex
Cardiovascular (CV)
The 4th heart sound (S4) is a low • S4 = hypertrophy S3 = dilation
frequency sound heard at the end • Children: S3 is normal, S4 is pathologic
of diastole just before S1. It is
due to ↓ LV compliance and is
often a/w RCM and LVH.
Pathophysiology
(Patp)
8
Pathophysiology
(Patp)
8
Pathophysiology
(Patp)
1
S3 is a low-freq sound occurring
immediately after S2 that's
commonly a/w ↑ ventricular ESV.
S3 freq occurs in the setting of
MR and systolic HF (e.g. DCM).
Cardiovascular (CV)
S3 gallop
• Bell over apex in left lat decubitus
position Due to
• Forceful, rapid filling of a ventricle that
has normal compliance
• Normal or even decreased filling rates
when ventricular compliance is low
• Blood flowing into an overfilled ventricle
with high end systolic volume
Tamponade
• Bulging of intraventricular septum into
LV > pulsus parasdoxus
Pathophysiology
(Patp)
12
PDA is characterised by a
continuous murmur heard best in
the left infraclavicular region w/
max intensity at S2. A small PDA
is often aSSx and is usually
detected incidentally during
routine cardiac auscultation. It
occurs most commonly in pts
born prematurely and those w/
cyanotic congenital heart disease.
PDA
• Continuous murmur with S2 splitting
during inspiration (physiologic)
• Max intensity at S2
Aortic regurg
• Associated with ascending aortic
aneurysm
Lutembacher Syndrome
• Continuous ASD murmur when coupled
with mitral valve obstruction
Cardiovascular (CV)
Pathophysiology
(Patp)
4
2100
Pulsus paradoxus
Asthma and COPD exacerbation
are the most frequent causes of
PP in the absence of significant
pericardial disease. β-adrenergic
agonists control acute asthma and
COPD exacerbations by causing
bronchial smooth muscle
relaxation via ↑ intracellular
cAMP.
2105
Aortic
regurgitation
AR causes a high-pitched,
blowing, diastolic murmur w/ a
decrescendo intensity pattern. The
murmur of AR due to aortic root
dilation is best heard at the right
upper sternal border, whereas the
murmur of AR due to valvular
pathology is best heard at the left
3rd ICS.
2106
Aortic stenosis
2107
S4
2108
Chronic heart
failure
2109
Patent ductus
arteriosus
2117
Ventricular septal A VSD is a/w a low-pitched,
defect
holosystolic murmur at the mid to
↓ left sternal border. It
accentuates during maneuvers
that ↑ afterload (eg, handgrip
maneuver). A small VSD is
usually aSSx and produces a
louder murmur due to higher
interventricular pressure gradient.
Cardiovascular (CV)
VSD
• Low pitched holosystolic murmur best
heart at left sternal border
• Accentuated with handgrip (increased
afterload shunts blood through VSD more)
ASD
• Mid systolic pulmonary ejection murmur
HCM
• Murmur will get quieter with increased
afterload or preload (decrease obstruction)
• Would with valsalva due to decreased
preload
AR
• Early diastolic murmur
• Increased with increased afterload
Pathophysiology
(Patp)
2
2124
Coronary blood
flow
The coronary sinus communicates
freely w/ the RA and will become
dilated 2° to any factor that
causes ↑ RA pressure. The most
common cause is pulm HTN,
leading to ↑ right heart pressures.
Cardiovascular (CV)
Right sided heart pressure will cause
coronary sinus dilation
• R heart HTN can be caused by pulmonary
HTN (especially in a midaged female)
Severe HTN
• Can cause aortic dissection
Pericardial effusion can cause coronary
sinus compression
Pathophysiology
(Patp)
9
11797
Wolff-Parkinson- WPW pattern is characterised by
White syndrome a shortened PR interval, widening
of the QRS complex, and slurred
initial upstroke of the QRS
complex (δ wave). It's caused by
an accessory pathway that
bypasses the AV node, causing
preexcitation of the ventricles. Pts
w/ WPW pattern can develop SSx
arrhythmia (e.g. AV re-entrant
tachycardia) due to re-entry of
electrical impulses thru the
accessory conduction pathway.
Cardiovascular (CV)
Pathophysiology
(Patp)
2
11833
Myocardial
infarction
The dominant RCA perfuses both
the inferior wall of the LV and
the majority of the RV. Proximal
occlusion can cause RV MI,
which Px w/ hypotension (↓ CO)
and distended jugular veins (↑
CVPs). The lungs will be clear on
auscultation and XR (lack of
pulm edema) unless concomitant
left-sided HF is also present.
Cardiovascular (CV)
Pathophysiology
(Patp)
18
11849
Primary
hypertension
PRA is a measure of the amount • Low Na diet > increased RAAS
of ATI generated per unit of time. • Renal art stenosis > increased RAAS
It provides a useful Ax of the
RAA axis. Factors that ↑ PRA
incl low Na+ intake and antiHTN Rx such as diuretics (e.g.
hydrochlorothiazide), ACEIs, and
ARBs (e.g. valsartan).
Cardiovascular (CV)
Pathophysiology
(Patp)
14
11851
Mitral
regurgitation
Regurg flow into the LA in acute
MR leads to ↑ LA pressure and ↑
LV EDV (preload). The lowresistance pathway also ↓ LV
afterload w/ a resulting ↑ in EF
but overall ↓ in forward SV. ↑ LA
pressure and ↓ CO result in pulm
oedema and severe hypotension,
respectively.
Cardiovascular (CV)
Mitral Regurg
• Acute: Increased preload, decreased
afterload, normal
contractile function, increased EF,
increased SV, pulmonary edema
• Compensated: increased preload, normal
afterload, normal contractile function,
increaed EF, normal SV, no pulmonary
edema
• Decompensated: increased preload and
afterload, decrease
contrile function, EF and SV, pulmonary
Pathophysiology
(Patp)
6
RV MI
• Due to RCA infarct > inferior wall
• Hypotension, JVD
• Clear lungs
• High central venous P, normal or low
PCWP, low CO
LV MI
• High central venous P, high PCWP, low
CO
13979
Septic shock
Septic shock causes widespread
arteriolar vasodilation, which
leads to a decrease in systemic
vascular resistance and a
compensatory increase in cardiac
output. Central venous pressure
and pulmonary capillary wedge
pressure are also decreased due to
pooling of blood in the dilated
veins Increased flow rates
through the peripheral capillaries
lead to incomplete oxygen
extraction by the tissues and high
mixed venous oxygen saturation.
Cardiovascular (CV)
Pathophysiology
(Patp)
6
14959
Pulmonary arterial Pulmonary arterial hypertension
hypertension
results from endothelial
dysfunction that leads to an
increase in vasoconstrictive,
proproliferative mediators (eg,
endothelin, thromboxane A2) and
a decrease in vasodilative,
antiproliferative mediators (eg,
nitric oxide, prostacyclin). The
relative imbalance in these
mediators leads to
vasoconstriction and intimal-wall
thickening with a consequent
increase in pulmonary vascular
resistance.
Cardiovascular (CV)
Pathophysiology
(Patp)
8
14966
Aortic stenosis
Angina often occurs in AS even
in the absence of obstr CAD. It
results from ↑ myocardial O2
demand due to an ↑ in LV mass
(i.e. concentric hypertrophy) and
ventricular wall stress.
Cardiovascular (CV)
Pathophysiology
(Patp)
8
15001
Vasospastic
angina
Vasospastic angina involves
hyperreactivity of coronary artery
smooth muscle. Pts are usually
young (age <50) and w/o
significant RFx for CAD; they
experience recurrent episodes of
chest discomfort that typically
occur during rest or sleep and
resolve w/i 15 min.
Cardiovascular (CV)
Pathophysiology
(Patp)
2
15180
Coronary artery
disease
Stable angina results from fixed
coronary artery stenosis that
limits blood flow to downstream
myocardium, preventing the
myocardial O2 supply from ↑
during exertion. Dobutamine
mimics the effects of exercise and
↑ myocardial O2 demand; it can
be used during stress testing to
provoke areas of ischemic
myocardium, which can be
recognized on imaging by a
localized and transient ↓ in
contractility (ie, wall motion
defect).
Cardiovascular (CV)
Pathophysiology
(Patp)
4
15199
Pulmonary arterial Pulm HTN can be recognized on
hypertension
PEx by a loud pulmonic
component of S2 and an
accentuated, palpable impulse at
the left stemal border (left
parasternal lift due to RV heave).
Cardiovascular (CV)
Pathophysiology
(Patp)
8
15241
Septic shock
Septic shock can Px w/ either
hyper- or hypothermia. The initial
disturbance is peripheral
vasodilation leading to ↓ SVR, ↓
CVP and ↓ PCWP. A
compensatory ↑ in sympathetic
drive causes an ↑ in CO; the
resulting high flow rates lead to
incomplete O2 extraction in the
tissues, resulting in high mixed
venous O2 saturation.
Cardiovascular (CV)
Pathophysiology
(Patp)
6
15269
Athlete's heart
Athlete's heart refers to
physiologic cardiac adaptations
that improve cardiac fxn in
response to high-lvl endurance
training. There's predominant
eccentric hypertrophy w/ a
smaller component of concentric
hypertrophy, leading to an overall
↑ in LV mass, enlarged LV cavity
size, ↑ LV wall thickness, and ↓
resting HR.
Cardiovascular (CV)
Pathophysiology
(Patp)
1
15310
Hypertrophic
cardiomyopathy
Pts w/ HCM may be aSSx and
often have a FHx of HCM or
SCD. Findings consistent w/
HCM incl an overall ↑ in LV
mass, ↓ LV cavity size w/
impaired diastolic fxn, LVH
predominantly affecting the
septum, and normal or ↑ LV EF.
Cardiovascular (CV)
Pathophysiology
(Patp)
9
15354
Aortic aneurysm
AAA is focal dilation of the
abdominal aorta above normal (or
>3 cm in diameter). It is generally
aSSx until aneurysm rupture,
which is frequently fatal. RFx
include age >65, smoking, and
male sex.
Cardiovascular (CV)
Pathophysiology
(Patp)
6
15528
Sick sinus
syndrome
aSSx LV systolic dysfxn is a
common stage in the progr of HF.
Neurohormonal mechs, incl the
SNS and RAAS, help maintain
the aSSx period by ↑ volume
retention and peri resistance to
maintain organ perfusion.
Although these mechs are
beneficial in the short term,
they're ultimately deleterious, ↑
hemodynamic stress and cardiac
remodelling that eventually lead
to DHF.
Cardiovascular (CV)
Pathophysiology
(Patp)
2
15574
Sick sinus
syndrome
SSS results from degeneration
(usually age-related) of the SA
node, leading to impaired
conduction and ↓ CO w/ SSx of
dyspnea, fatigue, lightheadedness,
presyncope, and syncope. ECG
typically demonstrates
bradycardia w/ sinus pauses
(delayed P waves), sinus arrest
(dropped P waves), and jxnal
escape beats.
Cardiovascular (CV)
Pathophysiology
(Patp)
2
15650
Acute heart failure Pts w/ DHF have ↑ LV EDP and ↓
CO that's most often 1arily due to
LV dysfxn. RA pressure (i.e.
CVP) is also ↑ in advanced HF
due to volume overload; RHF
(most often occurring 2° to LHF)
can also contribute to ↑ RA
pressure.
Cardiovascular (CV)
Pathophysiology
(Patp)
7
15651
Chronic heart
failure
The ventricular myocardium
secretes BNP in response to the
ventricular stretch and strain that
typically occurs w/ volume
overload. BNP, along w/ ANP
secreted by the atrial
myocardium, stimulates
vasodilation and salt and water
excretion to help relieve volume
overload.
Cardiovascular (CV)
Pathophysiology
(Patp)
12
15693
Long QT
syndrome
Congenital LQTS is commonly
caused by a mutation that slows
the delayed rectifier K current
that repolarizes the
cardiomyocyte AP. Certain Rx
(eg, macrolide Abx,
antipsychotics, antiemetics) also
slow the K repolarization current
and prolong the QT interval.
Excessive QT prolongation can
trigger serious cardiac arrhythmia
(ie, TdP), resulting in syncope or
SCD.
Cardiovascular (CV)
Pathophysiology
(Patp)
4
15729
Tricuspid
regurgitation
Severe TR can lead to right-sided
HF, evidenced by JVD,
hepatomegaly, lower extremity
edema, and the absence of pulm
edema. Permanent PM placement
can cause TR b/c the RV lead
passes through the TV orifice and
can disrupt valve closure.
Cardiovascular (CV)
Pathophysiology
(Patp)
3
16596
Aortic
regurgitation
A large, acute pulmonary
embolism causes a rapid increase
in right ventricular (RV) pressure
that leads to RV cavity
enlargement and RV dysfunction.
Thickening of the RV wall is not
seen in acute pulmonary
embolism, as there is no time for
compensatory hypertrophy to
occur in response to the increased
pressure load.
Cardiovascular (CV)
Pathophysiology
(Patp)
8
38
Vasospastic
angina
Prinzmetal (variant) angina is
Chx by episodic, transient atks of
coronary vasospasm (at rest and
at night), producing temporary
transmural myocardial ischemia
w/ ST-segment elevation.
Possible triggers are cigarette
smoking, cocaine/amphetamines,
and dihydroergotamine/triptans.
Tx includes tobacco/Rx cessation
and vasodilator Thx (eg, nitrates,
CCBs).
Prinzmetal angina
• Angina at rest or at night not related to
excursion
• Transient ST elevation
• Due to coronary vasospasm
• Dihydroergotamine: ergot alkaloid used
for migraines can precipitate
• Stimulates both alpha receptors and
serotonin receptor
• Prinzmetal can also be triggered by
cigarettes, cocaine/amphetamine, and
triptans
• Tx: CCB
Cardiovascular (CV)
Pharmacology
(Phar)
2
136
Nitrates
Nitrates (via conversion to NO)
activate guanylate cyclase and ↑
intracellular lvls of cGMP. ↑ lvls
of cGMP lead to myosin lightchain dephosphorylation,
resulting in vascular smooth
muscle relaxation.
Cardiovascular (CV)
Hypertensive emergency
• Tx: ntiroglycerine, nitroprusside Nitrates
• Becomes NO by SM cells of vasculature
> activated GC > increased cGMP >
decreased intracellular Ca > decreaed
activity of MLCK and dephosphorylation
of myosin light
chain > relaxation
Pharmacology
(Phar)
7
137
Angina
Pharmacologic nitrates (e.g.
nitroglycerin, isosorbide
mononitrate, isosorbide dinitrate)
are meta to NO and S-nitrothiols
in vascular smooth muscle cells,
leading to an ↑ in cGMP that
stims vasodilation. Large veins
are predominantly affected,
leading to ↑ venous capacitance
and ↓ venous return (preload),
which ↓ LV wall stress and
myocardial O2 demand to relieve
anginal SSx.
Cardiovascular (CV)
Nitroglycerine
• Venodilater (especially large veins)
Precapillary sphincters
• Respond to NE and epi
• Dilate with histamine, hypoxia, high
CO2, and acidosis
Arterioles: dilate with alpha1 blockers and
CCB
Pharmacology
(Phar)
1
138
Nitrates
Sublingual nitroglycerin is used
for rapid SSx relief in pts w/
stable angina. The 1° antiischaemic effect of nitrates is
mediated by venodilation w/ a ↓
in LV EDV and wall stress,
resulting in ↓ myocardial O2
demand and relief of angina SSx.
Cardiovascular (CV)
Nitroglycerin
• Venodatiol
• Decreased preload (decrease LV end
diastolic volume and pressure)
• Modest reduction in afterload
• Mild coronary artery dilation and reduced
coronary vasospasm
Beta blockers and CCB
• Decrease HR and contractility
Dihydropyridine CCB
• Coronary artery vasodilation > can cause
cornoary steal syndrome
Pharmacology
(Phar)
7
139
Nitrates
Isosorbide dinitrate has a low
bioavailability due to extensive
1st-pass hepatic metabolism prior
to release in systemic circulation.
Sublingual NG is absorbed
directly from oral mucosa into the
venous circulation and has a
higher bioavailability.
Cardiovascular (CV)
Sublingual nitro
• No first pass metabolism by liver
Isosorbide dinitrate
• Extensive first pass metabolism by liver >
low bioavailability > needs much high
doses than sublingual
Pharmacology
(Phar)
7
140
Nitrates
The main AEx seen w/ nitrate
Thx include h/a and cutaneous
flushing along w/ lightheadedness
and hypotension due to systemic
vasodilation.
Cardiovascular (CV)
Nitrates
• Venodilation primarily
• Adverse: HA, flushing, hypotension,
reflex tach
• Avoid in hypertophic cardiomyopathy,
RV infarct, and with Sildenafil
CCB and BB
• Delay AV node
Raynauds
• Amphetamines, ergotamine, chemo
Constipation
• Opioids, Fe supp, CCB, and
anticholinergics
Thiazide
• Gout
Nocturnal wheezing
• GERD or BB with pulmonary disease
Urinary retention
• TCA and antihistamines
Pharmacology
(Phar)
7
141
Hypertrophic
cardiomyopathy
The dynamic LVOT obstruction
that occurs in HCM worsens w/ ↓
LV volume, which can be caused
by ↓ in cardiac preload a/o
afterload. Therefore, Rx that ↓
venous return or SVR (DHP
CCBs, NG) should generally be
avoided.
Cardiovascular (CV)
HCM
• Systolic murmur that accentuates with
standing from supine
• Avoid: vasodilators (nifedipine, nitro,
ACE inhibitor) > decreased afterload
causing lower LV volumes; diuretics >
decrease LV preload
• Both causes increased outflow
obstruction
Pharmacology
(Phar)
9
142
Nitrates
Cardiovascular (CV)
Pts taking daily maintenance
Nitrate
nitrates need to have a nitrate-free • Rapid tolerance
period every day to avoid
• Thought to be due to decreased
tolerance to the Rx.
vascular sensitivity to nitrates and
increased sensitivity to endogenous
vasoconstrictors
• Pharmacokinetic drug interaction
• P450 inhibition or stimulation
Pharmacodynamic drug antagonism
• Ability of one drug (due to MOA) to
antagonize effect of another drug
Effect potentiation
• One drug's ability to increase the effect of
another drug
Pharmacology
(Phar)
7
143
Nitrates
Using nitrates together w/ PDEIs
used for ED and pulm HTN
causes a profound systemic
hypotension b/c they both ↑
intracellular cGMP which causes
vascular smooth muscle
relaxation. Their use together is
absolutely c/i.
Nitrates cre converted to NO by
vascular smooth muscles > NO
stimulates guanylyl cyclase to
production cGMP
• cGMP is degraded by
phosphodiesterase
• Nitrate + sildenafil = severe
hypotension
•Tachyphylaxis: tolerance causing
Cardiovascular (CV)
Pharmacology
(Phar)
7
145
Calcium channel
blocker
CCBs inhib the L-type Ca2+
channel on vascular smooth
muscle and cardiac cells. DHPs
(e.g. nifedipine, amlodipine)
primarily affect peripheral
arteries and cause vasodilation.
Non-DHPs (e.g. verapamil,
diltiazem) affect the myocardium
and can cause bradycardia and
slowed AV conduction.
CCB
• Dihydropyridine: nifedipine
• Arterial
• Nondihydropyridine: verapamil
• Myocardium
• Give nifedipine if pt in heart block or
bradycardia
Cardiovascular (CV)
Pharmacology
(Phar)
3
147
Digoxin
Digoxin toxicity typically
presents with cardiac arrhythmias
and nonspecific gastrointestinal
(nausea, vomiting), neurological
(confusion, weakness), and visual
symptoms. Elevated potassium is
another sign of digoxin toxicity
and is caused by inhibition of NaK-ATPase pumps.
Digoxin toxicity
• Arrhythmias
• Anorexia
• Nause and vomiting
• Abdominal pain
• Fatigue
• Confusion and weakness
• Color vision alterations
• Hyperkalemia
Cardiovascular (CV)
Pharmacology
(Phar)
4
148
Digoxin
Digoxin directly inhibs the Na-KATPase pump in myocardial
cells, leading to a ↓ in Na+ efflux
and an ↑ in intracellular Na+ lvls.
This ↓ the forward activity of the
NCX, causing ↑ intracellular
Ca2+ concentration and improved
myocyte contractility.
Cardiovascular (CV)
Digoxin
• Increases parasympathetic tone of AV
node
• Inhibits Na/K pump: decreases Na efflux
and K influx > decreased Ca efflux
(normally Na enters and Ca exits)
cAMP is the 2 messenger for excitation
contraction coupling
Pharmacology
(Phar)
4
149
Chronic heart
failure
Milrinone is a PDE-3 inhib that ↓
the degradation of cAMP to
provide 2 beneficial effects for
treating systolic HF. Ca2+ influx
into cardiomyocytes is ↑, which ↑
cardiac contractility. In addn,
Ca2+-myosin light chain kinase
interaction is ↓, which causes
vasodilation and ↓ cardiac preload
and afterload.
Milrinone and inamrinone
• PDE3 inhibitor > increased cAMP >
vasodilation and increased cardiac
contractility
ACE inhib
• Angioedema
Digoxin, beta blocker, CCB
• AV block
Cardiovascular (CV)
Pharmacology
(Phar)
12
150
Primary
hypertension
α1-blockers such as doxazosin,
prazosin, and terazosin are useful
for the Tx of both BPH and HTN.
Pts w/ CAD and HF along w/
HTN will benefit from
cardioselective β-blockers.
Hydrochlorothiazide is presently
the 1st-line Rx for the Tx of
essential HTN in the gen pop.
Cardiovascular (CV)
Alpha1 Blockers
• Adverse: orthostatic hypotension and
vertigo
• First dose is the wrost
Thiazides
• Adverse: hyponatremia
Eplerenone
• Less anti androgenic (decreased risk of
gynecomastia compared to spironolactone)
Pharmacology
(Phar)
14
153
Heart block
Common AEx of non-DHP CCBs
(eg, diltiazem, verapamil) include
constipation, bradycardia, AV
conduction block ((-)
chronotropic effect), and
worsening of HF in pts w/ ↓ LV
fxn ((-) inotropic effect).
Beta blockers and CCB can cause heart Cardiovascular (CV)
block and bradycardia
Veramapil and Diltiazem
• L type CCB > works on phase 4 in SA
and AV
• Adverse: constipation (verapamil >
diltiazem
Nifedipine
• Adverse: HA, dizziness, flushing and
peripheral edema Indapamide: thiazide
Terazosin
• Adverse: lightheaded and orthostasis
• Prazosin: PTSD
Pharmacology
(Phar)
2
154
Calcium channel
blocker
Amlodipine is a DHP CCB
commonly used as monoThx or in
combination w/ other agents for
Tx of HTN. Major AEx include
h/a, flushing, dizziness, and
peripheral edema.
Adverse HTN drugs
• Thiazide
• AKI, hyponatremia, hypoK,
hyperuricemia, high glucose and lipids
Nifedipine
• Peripheral edema (arteriolar dilation >
increase cap hydrostatic P)
• Decrease risk with ACE inhibitor
• Dizziness
Beta blockers
• Bronchospasm
• Bradycardia
• Fatigue
• Impotence
Eplerenone
• Less risk of gynecomastia
Cardiovascular (CV)
Pharmacology
(Phar)
3
155
Digoxin
Digoxin is used for ventricular
rate control in AF as it ↓ AV
nodal conduction by ↑
parasympathetic vagal tone.
Digoxin is also used in HF due to
its (+) inotropic effect. These
effects are accomplished via inhib
of the Na-K-ATPase pump.
Digoxin
• Rate control by enhancing vagal tone
inhibiting AV node conduction
• Great for A fib, A flutter with rapid
ventricular rate
Random
• Decreased AP duration > decreaed
refractory period > allow increased HR
• Delayed afterdepolarization: complete
repolarization but hyperexcitable due to
high intracellular Ca > proarrhythmic
Cardiovascular (CV)
Pharmacology
(Phar)
4
156
Digoxin
Digoxin tox presents w/
nonspecific GI (e.g. anorexia,
nausea, vomiting) and neuro (e.g.
fatigue, confusion, weakness)
SSx. Changes in colour vision are
a more specific, but rarer, finding.
Life-threatening ventricular
arrhythmias are the most serious
complication.
Digoxin OD
• GI issues first
• Confusion, weakness, fatigue
• Yellow color change
• Cardiac arrhythmias
• Risk of toxicity with hypokalemia,
hypovolemia, and renal failure
• Tx: Anti digoxin Ab
Cardiovascular (CV)
Pharmacology
(Phar)
4
159
Antiarrhythmic
drugs
For class I antiarrhythmics, Na+channel-binding strength is IC >
IA > IB. Use dependence
describes the phenomenon in
which higher HRs lead to ↑ Na+
channel blockade due to
cumulative blocking effects over
multiple cardiac cycles. Class IC
antiarrhythmics demonstrate the
most use dependence due to their
slow dissociation from the
receptor, and class IB drugs have
the least use dependence as they
rapidly dissociate.
Cardiovascular (CV)
Class 1 Antiarrhythmics exhibit use
dependence
• 1C > 1A > 1B
• The more they are used, the longer the
drug binds
1B (Lidocaine, mexiletine, tocainide)
• Bind less avidly to Na channels than
other class 1 drugs
• Fastest dissociation meaning very little
use dependence
• More selective for ischemic myocardium
do to reduced RMP delaying Na channel
transition from inactive to resting (1B
binds longer)
1C (Propafenone and flecainide)
1A (Disopyramide, quinidine, and
procainamide)
Pharmacology
(Phar)
12
160
Dyslipidemia
Niacin is used in the Tx of
hyperlipidemia. It ↑ HDL lvls and
↓ LDL lvls and triglycerides.
Niacin causes cutaneous flushing,
which is mediated by
prostaglandins and can be
diminished by preTx w/ aspirin.
Cardiovascular (CV)
Niacin
• Increases HDL
• Causes cutaneous flushing, warmth and
itching > mediated by PGE2 and PGD2
• Prophylaxis with aspirin 30min before
• Can also cause hyperglycemia and
hyperuricemia
Vancomycin
• Red man syndrome due to NOn IgE
mediated mast cell degranulation
Serotonin syndrome
• AMS, autonomic hyperactivity,
hyperreflexia and myoclonus
Substance P
• Mediated pain > topical capsaicin can
cause depletion of Substance P
Pharmacology
(Phar)
11
161
Drug induced
myopathy
Most statins are metabolized by
cytochrome P450 3A4, w/ the
exception of pravastatin.
Concomitant administration of Rx
that inhibit statin metabolism (eg,
macrolides) is a/w ↑ incidence of
statin-induced myopathy and
rhabdomyolysis. ARF is a
possible sequela of
rhabdomyolysis.
Cardiovascular (CV)
Pharmacology
(Phar)
3
315
Patent ductus
arteriosus
Cardiovascular (CV)
Pharmacology
(Phar)
4
CYP inducers
• Carbamazepine
• Phenobarbital
• Phenytoin
• Rifampin
• Griseofulvin
CYP inhibitors
• Cimetidine
• Ciprofloxacin
• Erythromycin (not azithromycin)
• Cyclosporine
• Azoles
• Grapefruit juice
• INH
• Ritonavir
All statin drugs (except pravastatin) are
metabolized by CYP3A4
• CYP inhibitor increases risk of
h
dh
i i
PDA is common in preterm
PDA
infants and presents w/ a
• Placental production of PGE2
continuous murmur, widened
• Continuous murmur
PPs, and SSx of CV strain.
• Wide PP and bounding pulses
Indomethacin or ibuprofen
• Metabolic acidosis
therapy can inhib PGE2 synthesis • Tachy, cardiomegaly and eisenmenger
and accelerate closure.
• Indomethacin closes PDA
IL 1: produced by macrophages
Cardiovascular (CV)
Permissiveness
• When 1 hormone allows another to exert
its maximal effect
• Cortisol and NE are permissive
(cortisol upregualted alpha1 receptors)
• If you ever see cortisol in this type of
question, go permissive regardless of other
drug
Additive
• When the the combined effect of 2 drugs
is equal to the sum of the individual drug
effects
Synergistic
• When the combined effect excessed the
sum of the individual drug effects
Tachyphylaxis
• Rapid development of tolerance
Pharmacology
(Phar)
4
Cardiovascular (CV)
OCP
• Estrogen: suppresses GnRH
• Progesterone: decreases risk of
endometrial cancer and thickens cervical
mucus
• Adverse: breakthrough menstrual
bleeding, breast tenderness, weight gain,
DVT, PE, stroke and MI
Never give to women
• Over 35 that smokes
• Previous thromboembolic event
• Hx of estrogen dependent tumor
• Hypertriglyceridemia
• Decompensated/active liver dz (impaired
steroid metabolism)
• Pregnancy
Cardiovascular (CV)
Amiodarone is 40% iodine by
Amio
weight. It can cause
• Corneal micro deposits
hypothyroidism due to ↓
• Optic neuropathy
production of thyroid hormone. • Peripheral neuropathy
Amiodarone can also cause
• Check LFT, PTF, TFT
hyperthyroidism due to ↑ thyroid
• Can cause ED
hormone synthesis or destructive
thyroiditis w/ release of
preformed thyroid hormone.
Pharmacology
(Phar)
3
Pharmacology
(Phar)
1
Initial empiric Tx of coagulase (-)
staphylococcal infection should
include vancomycin due to
widespread methicillin resistance,
esp. in nosocomial infections. If
susceptibility results indicate a
methicillin-susceptible isolate,
vancomycin can be switched to
nafcillin or oxacillin.
Cardiovascular (CV)
Mitral Valve replacement
• Infected with Staph epi
• 80% of Staph Epi is MRSA
• Tx: vancomycin
• Can add gentamicin or rifampin for
severe case
Native valve endocarditis
• If methicillin sensitive
• Tx: nafcillin
Random
mecA gene codes for methicillin resistance
> altered PBP
Pharmacology
(Phar)
15
MRBs (e.g. spironolactone,
eplerenone) improve survival in
pts w/ CHF and ↓ LV EF. They
shouldn't be used in pts w/
hyperkalaemia or renal failure.
Cardiovascular (CV)
Spironolactone and Eplerenone
• Block deleterious effect of aldosterone on
heart > regression of fibrosis and improved
ventricular remodeling
• Improves survival in CHF with low
EF
• Adverse: gynecomastia spironolactone >
eplerenone
Mannitol
• Used for high ICP and acute glaucoma
• Can cause pulmonary edema
Pharmacology
(Phar)
3
551
Dose response
curves
Cortisol exerts a permissive effect
on many hormones to help
improve the response to a variety
of stressors. For example, cortisol
increases vascular and bronchial
smooth muscle reactivity to
catecholamines and increases
glucose release by the liver in
response to glucagon.
577
Contraception
The absolute c/i to the use of
OCPs are: prior Hx of TE event
or stroke, Hx of an oestrogendependent tumour, women over
age 35yrs who smoke heavily,
hypertriglyceridaemia,
decompensated or active liver
disease (would impair steroid
meta), preg.
625
Amiodarone
645
Endocarditis
686
Aldosterone
antagonists
689
Primary
hypertension
Fenoldopam is a selective
peripheral dopamine-1 receptor
agonist. It is given IV to ↓ BP in
HTE, especially in pts w/ renal
insufficiency. Fenoldopam causes
arteriolar dilation, ↑ renal
perfusion, and promotes diuresis
and natriuresis.
Cardiovascular (CV)
Malignant HTN
• End organ damage: encephalopathy,
papilledema, AKI
Fenoldopam
• D1 agaonist
• D1 > Gs > arterial vasodilator (especially
renal vasodilation causing diuresis and
antriuresis)
• Great for pt with AKI
Hydralazine
• Direct arteriolar vasodilator
• Can cause reflex tach along with sodium
and fluid retention
Nitroglycerin
• Large vein dilator
Phenylephrine: alpha agonist
Cardiovascular (CV)
ARBs work by blocking ATII-1 RAAS Release
receptors, inhib the effects of
• Low Na to macula densa
ATII. This results in arterial
• Beta1 sympathetic input
vasodilation and ↓ aldosterone
• Low BP
secretion. The resulting fall in BP Ang 2 stimulates type 1 angiotensin 2
↑ renin, ATI, and ATII lvls. ARBs receptors to vasoconstrict and to
don't affect the activity of ACE, make/release aldosterone
and therefore they don't affect
ARBs (losartan)
bradykinin degradation and don't • High renin, ang 1, ang 2, low aldo normal
cause cough.
bradykinin
• Blocks vasoconstriction
Beta1 Blocker
• Low everything (decreases renin release)
Aliskirin
• High renin, low everything else
Spironolactone
• High everything
Pharmacology
(Phar)
14
691
Angiotensin
receptor blockers
Pharmacology
(Phar)
1
693
ACE inhibitors
ACEIs can cause significant 1stdose hypotension in pts w/
volume depletion (eg, from
diuretic use) or HF. To ↓ the risk
of 1st-dose hypotension, ACEI
Thx should be initiated at low
dosages.
Cardiovascular (CV)
ACE inhibitor
• First dose hypotension, especially those
who are volume depleted (on a diuretic) or
have HF
• Due to abrupt decrease in Ang 2
Pharmacology
(Phar)
7
697
Hyperkalemia
ACEIs block the conversion of
AT-I to AT-Il, thereby ↓
vasoconstriction and aldosterone
secretion. ↓ aldosterone leads to
K retention, which can cause
hyperkalemia, especially in pts w/
renal insufficiency and in those
taking other Rx that ↑ K lvls (eg,
ARBs, MRBs).
Cardiovascular (CV)
Drugs that cause hyperK
• Non selective Beta blockers: no K into
cells
• ACE inhibitors: no aldosterone
• ARBs: no aldosterone
• K sparing diuretics
• Digoxin: inhibit Na/K pump
• NSAIDs: reduced renin and aldosterone
secretion
Random Verpamil
• Adverse: constipation, peripheral edema
and bradycardia Indapamide (thiazide)
• hyperGLUC Amlodipine
• Reflex tachycardia and peripheral edema
Pharmacology
(Phar)
1
711
Dyslipidemia
Tx w/ statins causes hepatocytes
to ↑ their LDL receptor density,
leading to ↑ uptake of circulating
LDL.
Cardiovascular (CV)
Statins
• Decreased production of cholesterol
causes upregulation of LDL receptor
• Reduce risk of acute coronary event
• Anti inflammatory property, improves
endothelial dysfunction and stabilizes
atherosclerotic plaques
• Decrease TAG and minimal change of
FFA
• Biliary excretion of cholesterol decreases
in pt on statin (decrease cholesterol
production in liver)
Fibrates decrease VLDL production
Pharmacology
(Phar)
11
713
Antiplatelet
therapy
GI mucosal injury and bleeding
are the most common side effects
of aspirin. These are due
primarily to COX-1 inhib, which
results in impaired PG-dependent
GI mucosal defence and ↓ platelet
aggregation.
TIA
• Must treat BP, hypercholesterolemia
(statin) and anticoagulate (aspirin)
• Aspirin can cause GI bleeding (PPI
will reduce the risk of ulcer formation)
Sexual dysfunction
• SSRI, TCA, thiazide, spironolactone,
clonidine
Pioglitazone
• PPARgamma activater
• Increease risk of bladder cancer
Cardiovascular (CV)
Pharmacology
(Phar)
1
778
Drug induced
myopathy
The 1° side effects of statins
include myopathy and hepatitis.
Fibrates such as gemfibrozil can
impair hepatic clearance of
statins, ↑ the risk of severe
myopathy.
Pharmacology
(Phar)
3
780
Drug induced liver Common AEs of HMG-CoA
injury
reductase inhibs (statins) include
muscle and liver tox. Hepatic
transaminases should be checked
prior to initiating therapy and
repeated if SSx of hepatic injury
occur.
Pharmacology
(Phar)
2
781
Dyslipidemia
Although low HDL concentration
is a/w ↑ CV risk, the use of Rx to
↑ HDL lvls does not improve CV
outcomes. HMG-CoA reductase
inhibitors (statins) ↓ total
cholesterol and LDL lvls. Statins
are the most effective lipid-↓ing
Rx for 1° and 2° prevention of
CV events, regardless of baseline
lipid lvls.
• Statin + fibrate = myopathy
Cardiovascular (CV)
• Statin + ezetimibe = myopathy (less of a
chance than when a statin is given with a
fibrate)
• Bile acid sequestrant decrease statin GI
absorption Niacin
• Hepatotoxic, flushing, hyperglycemia,
hStatin i
i
Cardiovascular (CV)
• Hepatotoxic and myopathy
• Test LFT
Ezetimibe
• Hepatotoxic with statin
Niacin
• Decrease FA release, VLDL synthesis
and HDL clearance
• Flushing, hyperuricemia
Fibrate
• Activate PPARalpha and decrease
VLDL synthesis
• Myopathy and gallstones
Omega 3 FA
• Decreased VLDL and ApoB synthesis
Cardiovascular (CV)
Main lipid lowering drug effect
Statins
• Lowers LDL
• Best at decreasing risk of CAD
Fibrates (activated PPARalpha >
transcription factor for LPL)
• Lowers TAG
Bile acid sequesterants
• Lowers LDL but increases TAG
Niacin
• Increases HDL
• Ideally men over 40, women over 50
• Delivers cholesterol to liver via SRB1
Ezetimibe
• Lowers LDL
Omega 3 FA
• Lowers TAG
Exercise and weight loss
• Lowers TAG
Pharmacology
(Phar)
11
823
Myocardial
infarction
Fibrinolytic Thx for acute STEMI
is a reasonable reperfusion
technique for pts w/ no c/i to
thrombolysis. Fibrinolytic agents
such as alteplase bind to fibrin in
the thrombus (clot) and activate
plasmin, which leads to
thrombolysis. The most common
AEx of thrombolysis is
hemorrhage (eg, GI,
intracerebral).
Cardiovascular (CV)
MI
• PCI and fibrinolysis
• Tenecteplase, alteplase
• Risk of intrecerebral hemorrhage
• Alteplase converts plasminogen to
plasmin which hydrolyzes key bonds in the
fibrin matrix causing clot lysis
Reperfusion of ischemic myocardium
• Arrhythmias, myocardial stunning
(prolonged but reversible contractile
dysfunction) and myocyte death
Pharmacology
(Phar)
18
898
Antiarrhythmic
drugs
Adenosine causes
hyperpolarization of the nodal
PM to briefly block conduction
through the AV node, and it is
effective in the initial Tx of
PSVT. Common AEx include
flushing, chest burning (due to
bronchospasm), hypotension, and
high-grade AV block.
Cardiovascular (CV)
SVT
• Adenosine is DOC
• Adverse: flushing, bronchospasm, AV
block and sense of death
Amio
• SVT and V Tach
• Adverse: photodermatitis, blue/grey skin,
pulmonary fibrosis, hypo or hyperthyroid
Verapamil
• Constipation and gingivial hyperplasia
Pharmacology
(Phar)
12
899
Antiarrhythmic
drugs
Amiodarone (and other class III
and class IA antiarrhythmic
agents) causes lengthening of the
cardiac AP, which MFx as QT
interval prolongation on ECG.
QT prolongation caused by
amiodarone, in contrast to other
Rx, is a/w a very low risk of TdP.
Antiarrhymthmics 1A
• Slows AP and prolongs APD 1B
• No effect on AP
• Shortens APD 1C
• Slows AP
• No change on APD
2
• Slows SA and AV node > prolong
refractoriness
3
• No effect on AP
• Prolongs APD
• Amio: very low risk of torsades
4
• Slows SN and AV node > prolong
refractoriness
Adenosine
• Increase K efflux > delays AV
conduction
Dig
Cardiovascular (CV)
Pharmacology
(Phar)
12
900
Antiarrhythmic
drugs
Lidocaine is a class IB
antiarrhythmic Rx that tends to
bind to inactivated Na channels
and rapidly dissociates. As a
result, it is effective in
suppressing ventricular
tachyarrhythmias induced by
rapidly depolarizing and ischemic
myocardium.
Cardiovascular (CV)
MI
• Arrhythmias within first 48hr
• Amio is DOC
• Lidocaine is 2nd line
Class 1b
• Weakest Na channel blockers (fastest to
dissociated)
• Binds to inactivated Na channels (already
depol but not yet repol)
• Ischemic myocardium has higher than
normal RMP, dealying recovering (longer
time in inactivate state)
Digoxin
• Increase parasympathetic on AV node
Ibutilide
• Class 3
• Prolonged QT
Class 1a
• Binds to active Na channels
• Blocks K channels > prolonged QT
Pharmacology
(Phar)
12
901
Antiarrhythmic
drugs
Class III antiarrhythmic drugs
(e.g. amiodarone, sotalol,
dofetilide) predominantly block
K+ channels and inhib the
outward K+ currents during phase
3 of the cardiac AP, thereby
prolonging repol and total AP
duration.
Cardiovascular (CV)
Cardiomyocyte
• 0: Na
• 1: K (some inward Na)
• 2: Ca + K
• 3: K
• 4: Na/K pump
Class 3
• Amiodarone, sotalol, dofetilide) inhibits
K efflux
Adenosine: binds A1 receptor, increased K
efflux and decreased Ca influx
1A: quinidine, procainamide,
dysopryramide 1B: lidocaine
1C: flecainide
Pharmacology
(Phar)
12
948
Chronic cough
Cough is a very well recognized
AEx of ACEI Thx. Cough 2° to
ACEI Thx is Chx as dry,
nonproductive, and persistent.
The mechanism behind ACEI
induced cough is accumulation of
bradykinin, substance P, or
prostaglandins. b/c ARBs do not
affect ACE activity, they
theoretically should not cause
cough.
ACE inhibitor
• Increased bradykinin, substance P and
prostaglandins
• Bradykinin or substance P could
irritate the lung causing cough
Cardiovascular (CV)
Pharmacology
(Phar)
1
949
ACE inhibitors
Angioedema is a rare and serious
AE of ACEI therapy. ACEI ↑
bradykinin lvls, which ↑ vascular
permeability and lead to
angioedema. SSx include tongue,
lips, or eyelid swelling and, less
frequently, laryngeal oedema and
difficulty breathing. ACEI should
be discontinued in affected pts.
Angioedema
• C1 esterase inhibitor deficiency
• ACE inhibitor
• High bradykinin for both
Ige dependent mast cell degranulation
• Urticaria and pruritus
Ige INdependent mast cell degranulation
• Opiates, vancomycin
Cardiovascular (CV)
Pharmacology
(Phar)
7
1014
Dilated
cardiomyopathy
Anthracycline CTx agents (e.g.
doxorubicin, daunorubicin) cause
cardiotox mainly thru the
formation of anthracyclinetopoisomerase II DNA cleavage
complexes that affect healthy
cardiomyocytes. The cardiotox is
dependent on the cumulative dose
of anthracycline received, and it
manifests as DCM.
Doxorubicin (any rubicin)
• Generate ROS for chemo > also
cardiotoxic
• Swelling of sarcoplasmic reticulum is
early sign > loss of cardiomyocytes
(myofibrillar dropout)
• Dexrazoxane prevents DCM
Cor Pulmonale
• Accentuation and splitting of S2, JVD,
hepatomegaly
Restrictive CM
• Hemochromatosis, amyloidosis,
sarcoidosis, radiation, Loefflers,
endocardial fibroelastosis
HCM
• Beta myosin heavy chain mutation
Pericardial fibrosis
• Cardiac surgery, radiation theryapy or
virus
Cardiovascular (CV)
Pharmacology
(Phar)
8
1080
Peripheral
vascular disease
SSx Mx PVD includes a graded
exercise program and cilostazol.
Cilostazol is a PDEI that inhibs
platelet aggregation and acts as a
direct arterial vasodilator. Pts w/
PVD should also receive an
antiplatelet agent (aspirin or
clopidogrel) for 2° prevention of
CAD and stroke.
Cilostazol
• Used for peripheral claudication
• PDE3 inhibitor > high cAMP and PKA
• PKA inhibits platelet aggregation
(preventing plately shape
change and degranulation) and causes
vasodilation (preventing MLCK from
working)
Abciximab
• Ab against GP2b,3a
Heparin
• Potentiates antithrombin 3, inhibits
thrombin and Xa
Argatroban
• Direct thrombin inhibitor
• Use with HIT
Cardiovascular (CV)
Pharmacology
(Phar)
4
1082
Myocardial
infarction
In the fibrinolytic pathway, tPA
converts plasminogen to plasmin,
which then breaks down fibrin
clot. The administration of a tPA
analogue (eg, alteplase,
tenecteplase, streptokinase)
triggers fibrinolysis and can
restore myocardial perfusion in
pts w/ STEMI who cannot
undergo timely PCI.
Cardiovascular (CV)
• tPA, reteplase, tenecteplase are fibrin
specific fibrinolytics Contraindications:
hemorrhagic stroke, ischemic strong within
1 year, active internal bleeding, 180/100 or
suspected dissecting aneurysm
Reperfusion can like to arrhythmias
(usually benign)
Pharmacology
(Phar)
18
1118
Phosphodiesterase ANP, BNP, and NO activate
inhibitors
guanylyl cyclase and ↑ conversion
of GTP to cGMP. PDEIs (e.g.
sildenafil) ↓ the degradation of
cGMP. ↑ intracellular cGMP lvls
lead to relaxation of vascular
smooth muscle and vasodilation.
Cardiovascular (CV)
ANP and BNP
• Activate guanylyl cyclase > cGMP >
PKG > vasodilation
• NO activates cytosolic guanylyl
cyclase
Silfenafil
• PDE 5 inhibitor > more cGMP
• Severe hypotension if given with
nitrates
GABA
• Ligant gated ion channel
Vit D
• Intracellular receptor that translocated to
nucleus
Insulin
• Tyrosine kinase
IL 2
• JAK/STAT, also MAPK and
phosphoinositide 3• kinase
Pharmacology
(Phar)
1
1164
Sympathomimetic Blanching of a vein into which
agents
NE is being infused together w/
induration and pallor of the
tissues surrounding the IV site are
signs of NE extravasation and
resulting vasoconstriction. Tissue
necrosis is best prevented by local
injection of an α1 blocking drug,
such as phentolamine.
• NE drip for septic shock cause can
necrosis of skin
surrounding the IV site (vasoconstriction)
so give an alpha1 blocker (phentolamine)
Random
• Isoproterenol: beta2 agonist
Cardiovascular (CV)
Pharmacology
(Phar)
5
1166
ACE inhibitors
ACEIs and ARBs ↓ the risk of
CKD in pts w/ HTN and DM.
ACEIs ↑ lvls of bradykinin and
can cause nonproductive cough,
an effect not see w/ ARBs.
Cardiovascular (CV)
Pharmacology
(Phar)
7
1196
Myocardial
infarction
β blockers are used in AMI to ↓
morbidity and mortality by ↓ CO
and myocardial O2 demand. Noncardioselective β blockers (e.g.
propranolol, nadolol) can trigger
bronchospasm in pts w/
underlying asthma and COPD.
Cardioselective β blockers (e.g.
metoprolol) predominantly affect
β1 receptors and are preferred in
such pts.
B1 blockade
• Decreased HR, contractility, O2
consumption, renin release
• Adverse: worsen HF, brachycardia or
heart block
• Use in acute MI (improves long term
survival)
B2 blockade
• Vasospasm, bronchoconstriction,
decreased glycogenolysis and
gluconeogenesis, decreased K into cells
• Adverse: exacerbate COPD, worrse
peripheral artery disease, hypoglycemia
and hyperkalemia
Carvedilol and labetalol
• Combined alpha and beta blockers
• Safe in COPD
Cardiovascular (CV)
Pharmacology
(Phar)
18
1200
Anticoagulants
Warfarin is an oral anticoagulant
that inhibits the carboxylation of
vitamin K-dependent coagulation
factors II, VII, IX, and X. It is
used in AF, DVT, and pulm TE.
PT/INR should be monitored
regularly during Tx w/ warfarin.
aPTT is used for monitoring
UFH.
Warfarin
• Monitor PT/INR
• Use for A Fib, DVT, PE
• OD Tx: Vit K + FFP
• Adverse: skin necrosis (especially with
Protein C deficiency)
Hep
• Monitor PTT
• OD Tx: protamine
Cardiovascular (CV)
Pharmacology
(Phar)
8
1252
Primary
hypertension
Direct arteriolar vasodilators ↓ BP
but trigger reflex sympathetic
activation and stimulate the RAA
axis. This results in tachycardia
and edema. To counteract such
compensatory effects, these
agents are often given in
combination w/ sympatholytics
and diuretics.
Cardiovascular (CV)
Hydralazine, Minoxidil
• Arteriolar vasodilation
• Activates sympathetic nerve system >
tachycardia, increased contractility, CO
and RAAS release (retain water and salt)
• Usually given with sympatholytics and
diuretics
Beta blockers
• Cold feet and hands
Pharmacology
(Phar)
14
1342
Orthostatic
hypotension
Orthostatic hypotension is a
frequent cause of lightheadedness and syncope and is
defined as a ↓ in SBP
(>20mmHg) or DBP (>10mmHg)
on standing from the supine
position. Rx (α1-adrenergic
antagonists, diuretics), volume
depletion, and autonomic dysfxn
are common causes of orthostatic
hypotension.
Cardiovascular (CV)
Orthostatic hypotension
• Decrease in systolic > 20 or diastolic > 10
with standing
Normal sequence upon standing
• Low VR
• Low CO
• Drop in BP cause baroreceptor reflex
• Sympathetic response > alpha1 causing
vasoconstriction and beta1 causing
increased HR and contractility
Orthostatic hypotension causes
• Alpha1 blockers
• Diuretics
• Diabetes
• Parkinsons
• Hyperglycemia
Pharmacology
(Phar)
1
1343
Alpha agonists
α-adrenergic agonists ↑ SBP and
DBP by stimulating α1adrenoreceptors in the vascular
walls, causing vasoconstriction.
The ↑ systemic BP then causes a
reflexive ↑ in vagal tone,
resulting in ↓ HR and slowed AV
node conduction.
Cardiovascular (CV)
Alpha1 Agonist
• Vasoconstriction
• Mydriasis
• Initial increased contractility (countered
by increased reflex vagal tone > inhibit SA
node, decrease AV node conduction, and
decreased contractility)
• Increase internal urethral sphincter tone
Alpha2 Agonist
• Decreased BP
• Decreaesd IOP
• Decreased lipolysis
• Decreased NE release
• Increased platelet aggregation
Pharmacology
(Phar)
1
1344
Cardiogenic shock Dobutamine is a β adrenergic
agonist w/ predominant activity
on β1 receptors. It causes an ↑ in
HR and cardiac contractility,
leading to an ↑ in myocardial O2
consumption.
Dobutamine
• B1 agonist
• Used in refractory HF with severe LV
dysfunction and cardiogenic shock
• B1: Gs > positive ionotropy, positive
chronotropy, mild vasodilation
• Increase myocardial oxygen
consumption
• Will actually decrease PCWP due to
increased CO
Caught between a rock and a hard place >
stressing the heart is bad but the pt is in
cardiogenic shock
Cardiovascular (CV)
Pharmacology
(Phar)
1
1364
Sympathomimetic EPI ↑ SBP (α1 + β1) and HR
agents
(β1), and either ↑ or ↓ DBP
depending on the dose (either α1
or β2 predominates). PreTx w/
propranolol eliminates the β
effects of EPI (vasodilation and
tachycardia), leaving only the α
effect (vasoconstriction).
Phentolamine
• Non specific Alpha blocker
Phenylephrine
• Selective alpha agonist
Isoproterenol
• Non selective Beta agonist
Atropine
• Muscarinic antagonist
Cardiovascular (CV)
Pharmacology
(Phar)
5
1367
Sympathomimetic NE stim cardiac β1
agents
adrenoceptors, which ↑ cAMP
concentration w/i cardiac
myocytes and leads to ↑
contractility, conduction, and HR.
Peripheral vasoconstriction
occurs via stim of α1
adrenoreceptors in vascular
smooth muscle cells and
activation of an IP3 signalling
pathway.
Cardiovascular (CV)
Norepi
• Alpha1 > Alpha2 > Beta1
• Vasoconstrction via Alpha1 (Gq)
• Increase HR and contractility via Beta1
(Gs)
• HR usually goes down due to
baroreceptor reflex in response in increase
BP
Random
B2 in vascular SM: Gs resulting in
vasodilation
Pharmacology
(Phar)
5
1444
Beta blocker
poisoning
Pts who have OD'd on β blockers
should be Tx w/ glucagon, which
↑ HR and contractility
independent of adrenergic
receptors. Glucagon activates
GPCRs on cardiac myocytes,
causing activation of adenylate
cyclase and ↑ intracellular cAMP.
The result is Ca2+ release from
intracellular stores and ↑ SA node
firing.
Beta Blocker OD
• Decreased myocardial contractility,
bradycardia, AV block
• Tx: glucoagon > increase cAMP >
increase intracellular Ca > increase HR
and contractility
Cardiovascular (CV)
Pharmacology
(Phar)
1
1505
SLE
Procainamide and hydralazine
have the highest risk of causing
DILE, which is Chx by the
development of lupus-like SSx in
addition to (+) ANA and antihistone Abs. Unlike w/ SLE, antidsDNA Abs are rarely seen.
DILE
• Hydralazine
• Procainamide
• Isoniazid
• Minocycline
• Quinidine
• Slow acetylators are at a greater risk
for DILE
Amio adverse
• Thyroid dysfunction, lung fibrosis, liver
toxic, blue/grey discoloration,
photosensitivity
Lidocaine adverse
• tremor, drowsiness, change in mental
status, rarely seizures
Verapamil adverse
• Heart block, constipation, gingival
hyperplasia
Adenosine adverse
Cardiovascular (CV)
Pharmacology
(Phar)
7
1506
Antiarrhythmic
drugs
Sotalol has both β adrenergicblocking and class III
antiarrhythmic (K+ channelblocking) properties and is
occasionally used in Tx of AF.
Major AEs of sotalol include
bradycardia, proarrhythmia, and
most commonly TdP due to QT
interval prolongation.
Cardiovascular (CV)
Pharmacology
(Phar)
12
1507
Antiarrhythmic
drugs
Class III antiarrhythmic Rx
(amiodarone, sotalol, dofetilide)
predominantly block K channels
and inhibit the outward K
currents during phase 3 of the
cardiac AP, thereby prolonging
repolarization and total AP
duration.
Paroxysmal A Fib
• Rate control: class 2 and 4
• Rhythm control: class 1 and 3
• Prolonged QT: class 1a and 3
Diltiazem
• Prolonged PR interval
Metoprolol
• Decreased HR and contractility
Ranolazine
• Inhibts late phase inward Na flow
• Does not change HR or contractility,
decrease O2 demand
• Dofetilide: Class 3 antiarrhythmic
• K channel > internal reflectifer
Verapamil
• L type Ca channels
Cardiovascular (CV)
Pharmacology
(Phar)
12
1508
Antiarrhythmic
drugs
Class IC antiarrhythmic agents
(flecainide) block the fast Na+
channels responsible for
ventricular depol (phase 0),
prolonging QRS duration w/ little
effect on the QT interval. Class
IA and class III agents cause the
most QT prolongation.
Cardiovascular (CV)
• QRS complex = Ventricular
depolarization (phase 0) = Na entering cell
= Class 1 antiarrhythmics
Clase 1
• 1a: prolong QRS and QT
• 1b: no change in QRS or QT
• 1c: prolongs QRS and no change in QT
Pharmacology
(Phar)
12
1509
Antiarrhythmic
drugs
The class IA antiarrhythmics
Class 1 Na blockers
(quinidine, procainamide, and
• Moderate K channel blocking
disopyramide) are Na+ channel- 1A
blocking agents that depress
• Quinidine, Procainamide, Disopyramide
phase 0 depol. They also prolong • Prolong AP, ERP, and QT
repol due to moderate K+ channel- 1B
blocking activity, ↑ AP duration • Lidocaine, mexiletine
in cardiac myocytes.
• Shortens AP
1C
• Flecainide, propafenome
• No change on AP but prolongs ERP
Use dependence C > A > B
Adenosine
• Increase K efflux
Dig
• Increa PNS at AV node
Cardiovascular (CV)
Pharmacology
(Phar)
12
1565
Chronic heart
failure
Neurohormones (e.g. NE, ATII,
and aldosterone) play a large role
in the deleterious cardiac
remodelling that occurs in HF w/
↓ EF. ACEIs, ARBs, MRBs, and β
blockers ↓ mortality in these pts
by ↓ neurohormonal-mediated
cardiac remodelling.
Cardiovascular (CV)
CHF
• ACE inhibitor, ARBs, Beta blockers and
Spironolactone are only drugs to decrease
mortality rate
• Prevent deleterious cardiac
remodeling
Pharmacology
(Phar)
12
1780
Aging
Digoxin is a cardiac glycoside
that's predominantly cleared by
the kidneys. Elderly pts typically
exhibit age-related renal
insufficiency, even in the
presence of normal creatinine
lvls. The dose of digoxin must be
↓ in these pts to prevent tox.
Digoxin toxicity
• GI issues, visual changes
• Increse risk with age due to decreased
renal function (will see rise in Cr)
• Lean muscle mass is also important
consideration (not as important as renal
function)
Cardiovascular (CV)
Pharmacology
(Phar)
8
1828
Coronary artery
disease
Clopidogrel irreversibly blocks
the P2Y12 component of ADP
receptors on the platelet surface
and prevents platelet aggregation.
Clopidogrel is as effective as
aspirin in the prevention of CV
events in pts w/ coronary heart
disease.
Cardiovascular (CV)
Pharmacology
(Phar)
4
1836
Beta 2 agonists
Cardiovascular (CV)
Pharmacology
(Phar)
1
1944
Chronic heart
failure
Cardiovascular (CV)
Pharmacology
(Phar)
12
1947
Dose response
curves
Phenoxybenzamine is an
irreversible α1 and α2 adrenergic
antagonist that effectively ↓ the
arterial vasoconstriction induced
by NE. B/c phenoxybenzamine is
an irreversible antagonist, even
very high concentrations of NE,
such as those seen in
pheochromocytoma, can't
overcome its effects.
Irreversible Competitive Antagonist or
Noncompetitive Antagonist
• Same Km
• Lower Vmax
• Phenoxybenzamine: irreversible
Atropine, labetalol, phentolamine and
propanolol
• All reversible
Cardiovascular (CV)
Pharmacology
(Phar)
4
1948
Primary
hypertension
β blockers inhibit release of renin
from renal juxtaglomerular cells
through antagonism of β1
receptors on these cells.
Inhibition of renin release
prevents activation of the RAA
pathway, which results in ↓
vasoconstriction and ↓ renal Na
and water retention.
Cardiovascular (CV)
B1 blockers
• Decrease mycardial contractility and HR
• Decrease renin release
• Do not effect circulating level of
catecholamines
Pharmacology
(Phar)
14
Stable angina
• Tx: aspirin or clopidogrel for aspirin
intolerant pt
Apixaban
• Direct Xa inhibitor
• Prophylaxis for DVT, not CAD
Cilostazol
• Phosphodiesterase inhibitor
• Use: claudication
Eptifibatide
• Gp2b/3a inhibitor
NSAIDs and Celecoxib
Isoproterenol is a β1 and β2
Adrenergic agonist
adrenergic receptor agonist that Alpha1
causes ↑ myocardial contractility • Epi, NE, phenylephrine
and ↓ SVR.
Beta1
• Epi, Dopamine, Dobutamine,
Isoproterenol
Beta2
• Isoproterenol, terbutaline
Isoproterenol
• Non selective Beta agonist
• Increase cradiac contractility and HR,
vasodilate, uterine relaxation
Random Adenosine
Rx that have been shown to
HF
improve long-term survival in pts • Carvedilol, metoprolol, ACE inhibitors,
w/ HF due to LV systolic dysfxn ARBs, and aldosterone antagonists only
include β blockers, ACEIs,
medications to prove decreased mortality
ARBs, and aldosterone
Amio
antagonists.
• SVT and ventricular arrhythmias
2002
Primary
hypertension
Cardiovascular (CV)
TZDs ↑ serum Ca, uric acid, Glc, Thiazide adverse and mechanism
cholesterol, and triglyceride lvls. • HypoNa: inhibits Na/Cl in DCT
They ↓ serum Na, K, and Mg lvls. • HypoK: compensatory rise in renin and
aldo
• HyperCa: increased reabsorption in DCT
• HypoMg: decreased reabsorption in DCT
• Hyperglycemia and
hypercholesterolemia: decreased insulin
release and increased insulin resistance
• Hyperuricemia: increase reabsoprtion in
PCT
Pharmacology
(Phar)
14
2005
Aldosterone
antagonists
All diuretics except for the Ksparing class cause K loss by ↑
Na delivery to the late distal
tubule and cortical collecting
duct, where aldosterone-induced
Na reabsorption occurs at the
expense of K. K-sparing diuretics
(eg, spironolactone, amiloride)
act on the late distal tubule and
cortical collecting duct to
antagonize the effects of
aldosterone.
Pt with HF and hypokalemia
• Add spironolactone to spare K in late
DCT and early collecting duct
• Causes downregulation of ENaC and
Na/K pumps
• Amiloride and triamterene block ENaC
on principal cells
Cardiovascular (CV)
Pharmacology
(Phar)
3
2006
Antiarrhythmic
drugs
β blockers ↓ AV nodal
conduction, leading to an ↑ AV
nodal refractory period. This
correlates to PR interval
prolongation on an ECG.
Beta Blockers and non DHP CCB
• Prolong PR interval
T wave inversion
• Myocardial ischemia
Prlonged QT
• Class 1a and 3
• Macrolide and fluorquinolones
• Typical and Atypical antipsychotics
• TCA
• Ondonsetron
Cardiovascular (CV)
Pharmacology
(Phar)
12
6811
Septic shock
Phenylephrine is a selective α1
adrenergic receptor agonist that ↑
PVR and SBP and ↓ PP and HR.
Cardiovascular (CV)
Pharmacology
(Phar)
6
7640
Torsades de
pointes
TdP refers to polymorphic
ventricular tachycardia that
occurs in the setting of a
congenital or acquired prolonged
QT interval. TdP is most
commonly precipitated by Rx that
prolong the QT interval such as
certain antiarrhythmics (sotalol,
quinidine), antipsychotics
(haloperidol), and Abx
(macrolides, fluoroquinolones).
Prolonged QT
• Hypokalemia, hypomagnesemia
• Class 1A and 3 antiarrhythmics
• Macrolides and fluoroquinolones
• Methadone
• Antipsychotics
Class 2 and 4 antiarrhythmics
• Prolong PR interval
Cardiovascular (CV)
Pharmacology
(Phar)
1
8289
Beta blockers
β1 adrenergic receptors are found
in cardiac tissue and on renal
JGA cells, but not in vascular
smooth muscle. Selective
blockade of the β1 receptor (e.g.
w/ atenolol) leads to ↓ cAMP lvls
in cardiac and renal tissue w/o
significantly affecting cAMP lvls
in vascular smooth muscle.
Beta1 antagonist
• Decreaed cardiac cAMP
• Decreased JG cell cAMP
• No change is vascular smooth muscle
cAMP
• If Beta2 antagonist: decreased
vascular SM cAMP
Cardiovascular (CV)
Pharmacology
(Phar)
3
8291
Pharmacokinetics Clearance (CL) determines the
dose rate required to maintain a
steady-state plasma concentration
(Cpss): #6nov
Maintenance dose = Cpss x CL /
[Bioavailability fraction]
The bioavailability fraction = 1 if
administered IV.
Pharmacokinetics
• Half life = Vd x 0.7/ CL
• Maintenance dose = Steady state x CL x
dose interveral/ Bioavailability
• Loading dose = Vd x Steady state/
Bioavailability
Cardiovascular (CV)
Pharmacology
(Phar)
1
Cardiovascular (CV)
QRS typically slightly decreaes with
exercise
Flecainide (1C)
• Acvidly binds to Na channels responsible
for phase 0 > causing QRS prolongation
(especially with use)
Use dependence C>A>B
Dofetilide
• Class 3
• Prolongs QT
• Reverse dose dependence > slower the
HR the longer the QT
Cardiovascular (CV)
Nitrates are primarily
Nitrates
venodilators and increase
• Venous dilation (increased capacitance)
peripheral venous capacitance,
• Decreased LV end diastolic pressure
thereby reducing cardiac preload (decreased preload)
and left ventricular end-diastolic • Decreased systemic vascular resistance
volume and pressure. Nitrates
(modest arteriolar dilator)
also have a modest effect on
arteriolar dilation and cause a
decrease in systemic vascular
resistance and cardiac afterload.
Pharmacology
(Phar)
12
Pharmacology
(Phar)
7
Cardiovascular (CV)
Pharmacology
(Phar)
11
Cardiovascular (CV)
Dobutamine
• Predominant Beta1 agonist, weak Beta2
and Alpha1 agonist
• Weak vasodilation
Milrinone
• Phosphodiesterase inhibitor
Ranolazine
• Inhibits late phase inward Na channels in
ischemic myocardium > reduced Na/Ca
exchange > decrease O2 myocardial
demand
Pharmacology
(Phar)
5
Conduction impairment is
common w/ acute inferior wall
MI. Sinus bradycardia often
occurs due to nodal ischaemia
and an ↑ in vagal tone triggered
by infarction of myocardial
tissue; the ↑ vagal tone can be
counteracted by the antichol
effects of atropine.
Cardiovascular (CV)
Pharmacology
(Phar)
1
Dilated
cardiomyopathy
Trastuzumab is a mAb that blocks
HER2 to disrupt malignant cell
signalling and encourage
apoptosis. B/c HER2 helps
preserve cardiomyocyte fxn,
trastuzumab can cause cardiotox
that manifests as a ↓ in
myocardial contractility w/o
cardiomyocyte destruction or
myocardial fibrosis.
Cardiovascular (CV)
Pharmacology
(Phar)
8
Hypertrophic
cardiomyopathy
Many pts w/ HCM have poor
cardiac reserve (e.g. exercise
intolerance) due to LVOT
obstruction. This outflow
obstruction is worsened by ↓ LV
blood volume. β blockers ↓ HR
and LV contractility to ↑ LV
blood volume, ↓ LVOT
obstruction, and improve SSx.
Cardiovascular (CV)
Pharmacology
(Phar)
9
8869
Antiarrhythmic
drugs
Class 10 antiarrhythmics such as
flecainide are potent sodium
channel blockers that have
increased effect at faster heart
rates (use-dependence). This
makes them more effective at
treating tachyarrhythmias, but can
also cause prolonged QRS
duration (a proarrhythmic effect)
at higher heart rates.
11836
Nitrates
11844
Dyslipidemia
11925
Sympathomimetic Dobutamine is a β-adrenergic
agents
agonist w/ predominant activity
on β1 receptors and weak activity
on β2 and α receptors.
Stimulation of β2 receptors leads
to an ↑ production of cAMP and ↑
cytosolic Ca concentration. This
facilitates the interaction b/w
actin and myosin, resulting in ↑
myocardial contractility.
14780
Bradycardia
14844
15515
Fibrates lower TG lvls by
activating PPAR-α, which leads
to ↓ hepatic VLDL production
and ↑ LPL activity. Fish oil
supplements containing high
concentrations of ω-3 FAs ↓ TGs
by ↓ production of VLDL and
apoB.
• TAG > 500: use fibrates Fibrates
• Activate PPARalpha causes decresed
VLDL production and upregulates LPL
• Omega 3 FA: decrease VLDL
production, inhibits apolipoprotein B
synthesis
• Proprotein convertase subtilisin kexin 9
(PCSK9) inhibitor: Ab that reduces LDL
receptor degradation
144
Calcium channel
blocker
Contraction initiation in cardiac
and SMCs is dependent on
extracellular Ca influx through Ltype Ca channels, which can be
prevented by CCBs (eg,
verapamil). Skeletal muscle is
resistant to CCBs, as Ca release
by the SR is triggered by a
mechanical interaction b/w L-type
and RyR Ca channels.
Cardiovascular (CV)
Cardiac myocyte
• Depolarization of L type Ca channel on
plasma membrane allows Ca influx > Ca
binds to RyR2 on SR > Ca released
• Vascular SM have similar squence
after initial depolarization; Ca Calmodulin
facilitate actin myosin interaction
Skeletal muscle
• L type Ca channel directly interact with
RyR1 of SR > there is no influx of Ca
(physical interaction triggers Ca from SR
to be released)
• This explains why verapamil has no
effect of skeletal muscles
Physiology (Phys) 3
157
Natriuretic
peptides
ANP and BNP are released from
the atria and ventricles,
respectively, in response to
myocardial wall stretch due to
intravascular volume expansion.
These endogenous hormones
promote ↑ GFR, natriuresis. and
diuresis.
Physiology (Phys) 1
183
Coronary blood
flow
During ventricular systole, the
coronary vessels supplying the
LV are compressed by the
surrounding muscle. As a result,
the majority of LV blood flow
occurs during diastole. The
systolic ↓ in coronary blood flow
is greatest in the subendocardial
region, making this portion of the
LV most prone to ischemia and
infarction.
Cardiovascular (CV)
Nesiritide
• Recombinant BNP
• Used in decompensated CHF
• Activated GC > cGMP > vasodilation and
decreaed Na reabsorption in kidneys >
diuresis
TGFbeta
• Cell cycle arrest (used as tumor
suppressor), angiogenesis, and fibroblast
stimulation
Bradykinin
• Vasodilation of art, venodilation of veins
and pain
• Metabolized by ACE
Endothelin and Ang 2
• Vasoconstrictors
• Endothelin possibly released by Ang 2
• Right ventricle: relatively constant blood Cardiovascular (CV)
flow rate throughout cardiac cycle
205
Tetralogy of Fallot In pts w/ TOF, squatting during a
Tet spell ↑ SVR and ↓ right-toleft shunting, thereby ↑ pulm
blood flow and improving
O2ation status.
Cardiovascular (CV)
TOF
• Right to left shunt > cyanosis (tet spell) >
squating increases afterload (SVR)
reversing the shunt making it left to right
improving cyanosis
456
Primary
hypertension
Isolated systolic HTN (ISH; SBP
>140mmHg w/ DBP <90mmHg)
is due to age-related stiffness and
↓ in compliance of the aorta and
major peri arteries.
Isolated Systolic HTN
• Systolic > 140
• Diastolic < 90
• Caused by increased arterial stiffness,
increase CO due to AR, anemia or
hyperthyroid
Decreased CO
• Low systolic, diastolic and MAP
Decreased pulmonary residue volume
• Due to destruction of alveolar walls
Increased sympathetic tone or renal art
stenosis
• All BP variables go up
951
Coronary blood
flow
The high systolic intraventricular
pressure and wall stress of the LV
prevent myocardial perfusion
during systole; therefore, the
majority of LV myocardial
perfusion occurs during diastole.
Shorter duration of diastole is the
major limiting factor for coronary
blood supply to the LV
myocardium during periods of
tachycardia (e.g. exercise).
Cardiovascular (CV)
Myocardial perfusion during diastole
(decreased during exercise)
• Adenosine and NO are primary
vasodilators Contraction during systole
increase vornary pressure preventing blood
flow > highest at subendocardial region
• Diastolic pressure does not change during
exercise (TPR
decreases)
Cardiovascular (CV)
Physiology (Phys) 9
Physiology (Phys) 3
Physiology (Phys) 14
Physiology (Phys) 9
1510
Cardiac
physiology
An ↑ in effective SV or EF is
depicted on the LV pressurevolume relationship by widening
of the loop w/ a shift in the
isovolumic relaxation line to the
left (indicating less residual blood
volume in the ventricle at endsystole).
Cardiovascular (CV)
Physiology (Phys) 6
1511
Cardiac
physiology
Pressure-volume loops represent
the relationship b/w pressure and
volume in the LV during systole
and diastole. An ↑ in the
circulating volume ↑ preload (LV
EDV) and causes a rightward
widening of the pressure-volume
loop.
Cardiovascular (CV)
Cardiac loop
• Moving R verticle line of graph to the R
means increased preload
• Moving arc up means increased afterload
(decreases SV)
• Moving R ventricle line of graph to the L
means decreaed preload
• Moving L verticle line of graph to the L
means increased contractility (dobutamine)
• Moving L verticle line of graph to the R
means decreased contractility (MI)
Physiology (Phys) 6
1512
Hypovolemic
shock
Intravenous fluids increase the
intravascular and left ventricular
end-diastolic volumes. The
increase in preload stretches the
myocardium and increases the
end-diastolic sarcomere length,
leading to an increase in stroke
volume and cardiac output by the
Frank-Starling mechanism.
Cardiovascular (CV)
RAAS
• Increases HR and contractility
• Arteriolar bed constriction (maintains end
organ perfusion + shunts blood to vital
organs)
• Venous constriction to increase preload
• Water retention
Giving saline in hypovolemic shock
• Increase end diastolic sarcomere length >
increase contractility
• Decreae sympathetic NS > decrease HR
• Decrease RAAS
• Decrease TPR and cardiac contractility
VELOCITY
Physiology (Phys) 1
1513
Cardiac
physiology
The cardiac AP conduction speed Cardiac Conduction
is slowest in the AV node and
• Purkinje > atrial muscle > ventricular
fastest in the Purkinje system.
muscle > AV node
Conduction speed of the atrial
muscle is faster than that of the
ventricular muscle.
Cardiovascular (CV)
Physiology (Phys) 6
1515
Carotid
baroreceptors
Carotid sinus massage leads to an
↑ in PSNS tone causing
temporary inhib of SA node
activity, slowing of conduction
thru the AV node, and
prolongation of the AV node
refractory period. It's a useful
vagal manoeuvre for termination
of PSVT.
Cardiovascular (CV)
SVT
• Vagal maneuver: carotid massage,
valsalva, cold water immersion
Carotid massage
• Increased pressure > increased firing
carried by CN 9 > increased
parasympathetic via CN 10 and decreased
sympathetics (decrease SA node firing,
slows AV conduction and prolongs
refractory period)
• As pressure goes up, firing goes up
Physiology (Phys) 1
1516
Coronary blood
flow
Coronary autoregulation allows
coronary blood flow to be 1arily
driven by myocardial O2 demand
over a wide range of perfusion
pressures (60-140mmHg). It's
mostly accomplished by
alterations in vascular resistance
via release of adenosine and NO
in response to myocardial
hypoxia.
Heart extractions 70+% of O2 from the Cardiovascular (CV)
blood. In times of increased O2 demand,
vasodialtion is the only way to increase
O2 to the heart (mostly by local
metabolites
• Adenosine and NO are the most imporant
• eNOS makes NO from Arg
• NO release is stimulated by ACh, NE, 5•
HT, ADP, thrombin, histamine, bradykinin
and endothelin
• NO is also released in response to
pulsatile stretch and flow shear stress
(major regulator of flow mediated
vasodilation)
Beta2: NOT stimulated by NE
Physiology (Phys) 9
1517
Mitral stenosis
The classic cardiac auscultation
findings in MV stenosis include
an OS f/b a diastolic rumbling
murmur that is heard best over the
apex of the heart. On the
ventricular pressure-volume loop,
MV opening occurs at the point
b/w isovolumetric relaxation and
diastolic filling.
Cardiovascular (CV)
MS
• Opening snap with diastolic rumble
• Being shortly after S2
• Opening snap due to abrupt halt of leaflet
motion during mitral valve opening due to
fusion of the mitral valve leaflet tips
• The more severe the stenosis the
closer to S2
Physiology (Phys) 7
1518
AV fistula and
P/V curves
AV shunts can be congenital or
acquired; acquired forms can
result from medical interventions
or penetrating injuries. AV shunts
↑ preload and ↓ afterload by
routing blood directly from the
arterial system to the venous
system, bypassing the arterioles.
High-volume AV shunts can
eventually result in high-output
cardiac failure.
AV fistula
• Pulsatile mass with thrill on palpation
(constant bruit)
• Increase preload, increase CO, decrease
afterload
Cardiovascular (CV)
Physiology (Phys) 1
1528
Pulmonary blood
flow
The circulatory system is a
continuous circuit, and therefore
the volume output of the left
ventricle must closely match the
output of the right ventricle. This
balance is necessary to maintain
continuous blood flow through
the body and exists both at rest
and during exercise.
The pulmonary and systemic
circulations have the same blood flow
per minutes
• The only exception is the bronchial
circuit, which supplies that lungs and
drains to the left atrium (technically
increasing
systemic output more than pulmonary but
less than 5%)
Cardiovascular (CV)
Physiology (Phys) 2
1529
Cardiac
physiology
The Fick principle can be applied
to calculate CO using the rate of
O2 consumption and the AV O2
content difference:
CO = rate of O2 consumption /
AV O2 content difference
• CO = SV x HR
• CO = rate of O2 consumption/ Art
Venous O2 difference MAP = CO x TPR
• Blood O2 content = (O2 bind capacity x
% sat) + dissolved O2
Cardiovascular (CV)
Physiology (Phys) 6
1530
LV volume and
pressure
Ventricular pressure and volume
curves allow 1 to ID the phases of
the cardiac cycle and to determine
the exact time of opening and
closure of the cardiac valves. The
AV opens when LVP exceeds the
central aortic pressure at the end
of isovolumetric contraction.
Cardiovascular (CV)
Physiology (Phys) 1
1531
Cardiac
physiology
In cardiac pacemaker cells, phase
0 depol is mediated by an inward
flux of Ca2+. This differs from
phase 0 of cardiomyocytes and
Purkinje cells, which results from
an inward Na+ current.
Cardiovascular (CV)
Physiology (Phys) 6
1557
Heart sounds
The 3rd heart sound (S3) is a lowfrequency sound occurring during
early diastole after S2. LV gallops
(S3 a/o S4) are best heard w/ the
bell of the stethoscope over the
cardiac apex while the pt is in the
left lateral decubitus position at
end expiration.
Cardiovascular (CV)
CHF
• S3 due to big floppy heart
• S3 is the due to blood hitting ventricular
walls
• Normal is kids and young adults
• If heard over 40, this ventricualr dilation
• Best heard with bell of stethoscope over
cardiac apex with pt in L lat decubitus
position at END EXPIRATION
Random
Amily nitrite: decreased VR
Furosemide: decreased end systolic
ventricular volume Valsalva and abrupt
standing: decreased VR
Physiology (Phys) 1
1589
Physical exercise
Cardiovascular (CV)
The cardioresp response to
With exercise
exercise includes ↑ HR, CO, and • Normal arterial O2 and CO2
RR in order to balance the ↑ total • Decreased venous O2 and increased CO2
tissue O2 consumption and CO2
production. These coordinated
adaptations result in relatively
constant ABG values whereas
venous O2 is ↓ and venous CO2
is ↑.
Physiology (Phys) 2
1591
Mitral stenosis
Under normal circumstances,
PCWP closely reflects LA and
LV EDP. MS leads to an ↑ in the
LA pressure that is reflected as ↑
PCWP during pulm artery
catheterization. LV filling may be
normal, resulting in an ↑ pressure
gradient b/w the LA and LV
during diastole.
Physiology (Phys) 7
1609
Carotid sinus
hypersensitivity
• Swan Ganz catheter: PCWP = LA
Cardiovascular (CV)
pressure
MS
• High LA pressure
• Normal ventricular pressure
AS
• High LVEDP and PCWP
Tamponade
• Equalization of pressure in all chambers
(elevated)
Dilated cardiomyopathy
• Systolic dysfunction > high LVEDP and
PCWP
Restrictive cardiomyopathy
• Diastolic dysfunction > high LVEDP and
Cardiovascular (CV)
The carotid sinus is a dilation of Carotid Body Baroreceptor
the ICA located just above the
• Decreased BP > decreased firing via CN
bifurcation of the CCA. The
9 (Hering nerve which synapses on
carotid sinus reflex has an
medulla) > increased sympathetic stim
afferent limb that arises from the • High BP > high firing via CN 9 >
baroreceptors in the carotid sinus increase parasympathetic stim via CN 10
and travels to the vagal nucleus Aortic Arch Baroreceptor
and medullary centers via the
• CN 10 is afferent limb
glossopharyngeal nerve (CN IX); • More responsive to high BP than low BP
the efferent limb carries
(high pressure system)
parasympathetic impulses via the
vagus nerve (CN X).
1621
Renal artery
stenosis
Blood flow is directly
proportional to the vessel radius
raised to the fourth power.
Resistance to blood flow is
inversely proportional to the
vessel radius raised to the fourth
power.
• Flow = (P1 P2/ viscosity x L) x r^4
• If you decrease the radius by 2 > flow
will increase by 16
Cardiovascular (CV)
Physiology (Phys) 9
1622
Physical exercise
Exercising muscles can receive
up to 85% of the total CO during
periods of strenuous activity.
Although sympathetic discharge
during exercise causes ↑ CO and
splanchnic vasoconstriction,
there's only a modest ↑ in mean
BP as vasodilation w/i active
skeletal muscles significantly ↓
the total SVR.
Cardiovascular (CV)
Exercise
• Increased sympathetic stimulation >
increase HR, SV, CO, LV diastolic
volume, LV diastolic P, pulmonary artery
systolic P, contraction of all arterioles
besides the working muscles
causing increase systolic BP,
DECREASED systemic vascular resistance
• Muscles release adenosine, K, ATP,
CO2 and lactate that
cause vasodilation
Physiology (Phys) 2
1624
Cardiac output and MI causes a sharp ↓ in CO due to
venous return
loss of fxn of a zone of
myocardium. On a cardiac fxn
curve, MI would ↓ both the slope
and the maximal height of the
line.
Cardiovascular (CV)
CO vs VR grpah
• When VR crosses x axis: mean systemic
filling pressure (measure of degree of
filling of the circulatory system relative to
the circulatory capacity)
• Change in blood volume to move x
axis intercept
• Increase TPR will shift VR curve
down and decrease CO
• Decreased TPR will shift VR curve up
and increase CO
• Decreased contractility will only shift
CO down
• Chronic anemia will in contractility
and thus CO
• Anaphylaxis: increase contractility but
decrease VR
Physiology (Phys) 2
Physiology (Phys) 1
1625
Cardiac output and A chronic AV shunt would ↑ CO
venous return
b/c of ↑ sympathetic stimulation
to the heart, ↓ TPR, and ↑ venous
return. It would also cause the
venous return curve to shift to the
right b/c the circulating blood
volume is ↑ through renal
retention of fluids and b/c venous
pooling is ↓ by the ↑ sympathetic
tone.
Cardiovascular (CV)
•
• Will see an increase in cardiac out and
decreased TPR
• On graph > Increased contractility,
increased venous return, increased CO and
same right atrial pressure (end diastolic
volume)
• Acute would be the same but venous
return would cross x axis at same place as
normal
Phenylephrine
• Increased TPR > decreased CO (higher
afterload and less preload)
Anaphylaxis
• Significant drop in venous return
Physiology (Phys) 2
1652
Diastolic
dysfunction
Na nitroprusside is a short-acting
agent that causes balanced
vasodilation of the veins and
arteries to ↓ both LV preload and
afterload. The balanced
vasodilation allows for
maintenance of SV and CO at a ↓
LV pressure (↓ cardiac work).
•
• Arterial and Venous dilation > will see
drop in afterload and preload
Increase contractility
• Larger SV > less LV end systolic vol
Nitroglycerin
• Venous dilation > decreased preload
Cardiovascular (CV)
Physiology (Phys) 4
1653
Cardiac pressure
range
Right-sided pressures in the heart
are lower than left-sided
pressures due to lower resistance
in the pulm vasculature. RV
diastolic pressure is similar to
RA/CVP (1-6 mm Hg), whereas
pulm artery diastolic pressure is
slightly higher (6-12 mm Hg) due
to resistance to flow in the pulm
circulation.
Pressure readings
• SVC and RA: 1 6mmHg RV: 25/2
• Pulmonary artery: 25/10
• Pulmonary artery wedge and LA: 812
LV: 120/10
Cardiovascular (CV)
Physiology (Phys) 1
1661
Aortic
regurgitation
AR causes an ↑ in total SV w/
abrupt distension and rapid falloff
of peripheral arterial pulses,
resulting in a wide PP. This leads
to bounding peripheral pulses and
head bobbing w/ each heartbeat.
Cardiovascular (CV)
Aortic Regurg
• Eccentric hypertrophy with increeased
LV end diastolic volumes
• Blowing decrescendo diastolic murmur
• Hyperdynamic pulses (wide PP, bound
femoral and carotid pulses, head bobbing)
AS
• Pulsus parvus et tardus
Coarctation
• HTN in upper, diminshed and delayed
pulses in lower
Physiology (Phys) 8
1782
Pericardial
effusion
PP refers to an exaggerated drop
(>10 mm Hg) in SBP during
inspiration. It is most commonly
seen in pts w/ CT but can also
occur in severe asthma, COPD,
hypovolemic shock, and
constrictive pericarditis.
Cardiovascular (CV)
Cardiac tamponase
• Hypotension, JVD, muffled heart sounds
• Electical alternans
• Pulsus paradoxus (pericardial fluid limits
RV expansion exacerbated by inspiration,
pushes septum into LV decreaed SV)
Pulsus alternans: variation in pulse
amplitude due to LV dysfunction
Dicrotic pulse: severe systolic dysfunction
and high TPR Hyperkinetic pulse: aortic
regurg, AV fistula or thyrotoxicosis Pulsus
parvus et tardus: fixed LV outflow tract
obstruction (AS)
Physiology (Phys) 1
1931
Muscle structure
and physiology
Ca efflux from cardiac cells prior
to relaxation is primarily
mediated via an Na/Ca exchange
pump and SR Ca-ATPase pump.
Cardiovascular (CV)
Cardiac contraction
• Voltage dependent (L type) Ca2+
channels open during phase 2 > Ca enters
> Ryanodine receptor release Ca from SR
> positive feedback
Cardiac relaxation
• 3 Na/1 Ca exchange pump and SERCA
(ATP pump) remove Ca from cytoplasm
and return it to the SR
Calmodulin
• Excitation contraction coupling in smooth
muscles
Physiology (Phys) 1
1973
Antiarrhythmic
drugs
Class IV antiarrhythmics (eg,
verapamil, diltiazem) are
commonly used to prevent
recurrent nodal arrhythmias (eg,
PSVT). They work by blocking
Ca channels in slow-response
cardiac tissues, slowing phase 4
(spontaneous depolarization) and
phase 0 (upstroke). This ↓
impulse conduction velocity in
the SA and AV nodes.
Cardiovascular (CV)
Cardiac Node AP
• Phase 4: Na enters during diastolic
depolarization > later transient inward Ca
current
• Phase 0: threshold met > more Ca influx
• Verapamil is a non DHP CCB that
slows diastolic depolarization during late
phase 4 and all of phase 0
Class 1 and Class 4
• Raise threshold potential of cardiac fast
and slow response tissues, respectively
Class 1B
• Shorts AP
Class 1A, 3 and 4
• Increase refractory period
Class 4
• Decrease intracellular Ca in cardiac
MYOCYTE
Physiology (Phys) 12
1974
Cardiac AP
The cardiac myocyte AP consists Mycocardial depolarization
of rapid depolarization (phase 0), • Phase 2: L type DHP Ca channels open
initial rapid repolarization (phase
1), plateau (phase 2), late rapid
repolarization (phase 3), and
resting potential (phase 4). The
AP is a/w ↑ membrane
permeability to Na and Ca and ↓
permeability to K.
1975
Cardiac
physiology
1976
Pacemaker
potential
Cardiovascular (CV)
Physiology (Phys) 1
The phase 4 slow depolarization
in cardiac PM cells occurs due to
the closure of repolarizing K
channels, the slow influx of Na
through funny channels, and the
opening of T-type Ca channels.
ACh and adenosine ↓ the rate of
spontaneous depolarization in
cardiac PM cells by prolonging
phase 4.
Cardiovascular (CV)
Cardiac Nodes
• Phase 4: Na influx and little K efflux
through funny channel >
• 50 opens t type Ca channels open > 40 L
type Ca channels open
•Phase 0: begins at 40, Ca depolarizes cell
fully Phase 3: L type Ca channels close, K
channels open Adenosine
• Binds A1 receptors increasing K efflux
during phase 4 slowing
HR
• Also inhibits L type Ca channels further
prolonging depolarization
• ACh slows phase 4
NE
• Facilitates L type Ca channel opening
increasing depolarization
Physiology (Phys) 6
Cardiac pacemaker impulse
generation normally occurs in the
SA node, which has the fastest
firing rate of all conductive cells.
The cells in other areas of the
conduction system (eg, AV node,
bundle of His, and Purkinje
fibers) may serve as pacemakers
if normal impulse conduction is
impaired.
• SA node: 60 100 bpm AV node: 45 55
bpm Bundle of His: 20 bpm Purkinje: 10
bpm
• In 3rd degree heart block: AV node is
responsible for ventricular heart rate
Cardiovascular (CV)
Physiology (Phys) 1
Physiology (Phys) 5
1977
Atrial fibrillation
AF occurs due to irregular,
chaotic electrical activity w/i the
atria and Px w/ absent P waves,
irregularly irregular R-R
intervals, and narrow QRS
complexes. The AV node
refractory period regulates the
number of atrial impulses that
reach the ventricle and determines
the ventricular contraction rate in
conditions where the atria
undergo rapid depolarization.
Cardiovascular (CV)
A Fib
• Absent P waves
• Irregularly irregular r R interval
• Narrow QRS
• AF leads to electrical remodeling of the
atria with the development of shortened
refractory periods and increased
conductivity (A fib begets A fib)
• Ventricular rate is determined by AV
node refractory period
Brundle branch conductivity: determine
QRS complex
• If wide QRS, look at lead 1: if positive
then RBBB, if negative then LBBB
1978
Chronic heart
failure
Atrial natriuretic peptide (ANP)
and brain natriuretic peptide
(BNP) are secreted by atrial and
ventricular cardiomyocytes in
response to myocardial stretching
induced by hypervolemia. These
natriuretic peptides inhibit the
renin-angiotensin-aldosterone
system and stimulate peripheral
vasodilation and increased
urinary excretion of sodium and
water. Neprilysin inhibitors (eg.
sacubitril) prevent the
degradation of ANP and BNP,
enhancing their beneficial effects
in heart failure.
Neprilysin (Sacubitril)
• Metalloprotease that inactivates ANP,
glucagon, bradykinin
ANP
• Activates guanylate cyclase
• Kidney: dilates afferent art, inhibits Na
reabsorption in PCT and inner medullary
collecting duct, inhibits renin release
• Adrenal: decreased aldo release
• Blood vessel: vasodilation and increase
permeability
Duodenal mucosa
• Gastrin, secretin and CCK
1983
Tricuspid
regurgitation
A holosystolic murmur that ↑ in
intensity on inspiration most
likely represents TR. The other
holosystolic murmurs (which are
2° to MR or a VSD) do not
typically ↑ in intensity during
inspiration.
Cardiovascular (CV)
Ho
• Tri regurg: loudens on inspiration
• Mitral regurg and VSD: do not get louder
on inspiration (no change)
Physiology (Phys) 3
2009
Coronary blood
flow
Myocardial oxygen extraction
exceeds that of any other tissue or
organ; therefore, the cardiac
venous blood in the coronary
sinus is the most deoxygenated
blood in the body. Due to the high
degree of oxygen extraction,
increases in myocardial oxygen
demand can only be met by an
increase in coronary blood flow.
Myocardial muscles extract the largest
amount of O2 of any tissue
• Thus O2 demand is tightly coupled
with coronary blood flow (Adenosine and
NO are predominant vasodialtors)
Cardiovascular (CV)
Physiology (Phys) 9
2055
Atrial fibrillation
Palpitations refer to a subjective
sensation/awareness of the
heartbeat due to rapid arrhythmias
or forceful ventricular
contractions. AF is the most
common cause of an irregularly
irregular rhythm and is detected
on ECG by an absence of
organized P waves and varying RR intervals.
A fib
• Absent P waves
• Varying r R interval
• Irregularly irregular
• Can be seen with excessive alcohol
consumption
Ventricular hypertrophy
• High QRS voltage in precordial leads
Cardiovascular (CV)
Physiology (Phys) 5
Cardiovascular (CV)
Physiology (Phys) 12
8293
Supine
hypotension
Pregnant women > 20 wks
gestation can experience
compression of the IVC by the
gravid uterus while in the supine
position. This ↓ venous return and
CO, which can result in
hypotension and syncope.
Cardiovascular (CV)
Supine hypotension
• Usually in late pregnancy due to
compression of IVC decreasing venous
return
• Peripheral neuropathy can cause
orthostatic hypotension due to decreased
autonomic function (diabetes)
• Hypotension in early pregnancy due to
reduced TPR Vasovagal syncope caused by
concomitant withdrawal of
sympathetic efferent and enhanced
parasympathetic activity
(bradycardia, vasodilation and orthostasis)
Physiology (Phys) 1
8546
Chronic heart
failure
The ↓ CO in HF triggers
compensatory activation of the
SNS and RAAS, resulting in
vasoconstriction (↑ afterload),
fluid retention (↑ preload), and
deleterious cardiac remodelling.
These mechs perpetuate a
downward spiral of cardiac
deterioration, leading to SSx
DHF.
Cardiovascular (CV)
Acute decompensated HF
• Reduced CO and high ventricular
pressure
• Increase sympathetic (increased HR and
contractility, RAAS, release of ADH)
Adverse
• Increased afterload worsens CO
• High RAAS leads to volume overload
• Deleterious cardiac remodeling due to
hemodynamic stress and neurohumoral
stimulation
Physiology (Phys) 12
8563
Arginine in NO
production
Nitric oxide is synthesized from
arginine by nitric oxide synthase.
As a precursor of nitric oxide,
arginine supplementation may
play an adjunct role in the
treatment of conditions that
improve with vasodilation, such
as stable angina.
Cardiovascular (CV)
Endothelium dependent vasodilation
• ACh, bradykinin or shear stress increases
endothelial Ca > increased eNOS (take
Arg + O2 + NADPH > NO + citrullin) >
NO activates GC > high cGMP > activated
PKG which decreased Ca > vasodilation
Physiology (Phys) 1
11745
Chronic heart
failure
Neprilysin is responsible for the
breakdown of the natriuretic
peptides and AT-II; therefore,
inhibition of neprilysin ↑ the
activity of these peptides. For Tx
of HF, neprilysin inhibition is
combined w/ AT-II receptor
blockade to optimize the (+)
effects of the natriuretic peptides
(eg, vasodilation, diuresis) while
blocking the (-) effects of AT-II
(eg, vasoconstriction, fluid
retention).
BNP
• Released by ventricles
• Cause diuretic, natriuretic and
vasodilatory effect
• Neprilysin: metalloportease that cleaves
and inactivated peptide
• If inhibits, increased natriuretic
peptides (helpful for HF)
12187
Endocarditis
14743
Atrial fibrillation
Cardiovascular (CV)
Physiology (Phys) 12
During the normal cardiac cycle,
central aortic pressure is higher
than RV pressure during systole
and diastole. Consequently, an
intracardiac fistula b/w the aortic
root and RV will most likely
demonstrate a left-to-right cardiac
shunt as blood continuously flows
from the aortic root (high
pressure) to the RV (low
pressure).
Cardiovascular (CV)
Physiology (Phys) 15
AF is recognized by an irregularly
irregular rhythm w/ variable R-R
intervals and absence of P waves
on ECG. The development of AF
most commonly involves ectopic
electrical foci in the pulm veins
that trigger fibrillatory conduction
in abnormal (remodeled) atrial
tissue.
Cardiovascular (CV)
Physiology (Phys) 5
14745
Atrial flutter
Atrial flutter demonstrates rapid
and regular atrial activity in a sawtoothed pattern (flutter or F
waves) on ECG. Typical atrial
flutter is caused by a large reentrant circuit that traverses the
cavotricuspid isthmus of the RA,
which is the target site for
radiofrequency ablation.
Cardiovascular (CV)
Physiology (Phys) 1
14976
Aortic
regurgitation
AR causes a rapid fall in aortic
pressure during diastole w/ an ↑
in LV EDV and a compensatory ↑
in SV. These hemodynamic
changes create Chx pressure
changes, including ↓ aortic
diastolic pressure, ↑ aortic
systolic pressure, and ↑ LV
diastolic and systolic pressures.
Cardiovascular (CV)
Physiology (Phys) 8
15391
Diastolic
dysfunction
Prolonged systemic HTN leads to
concentric LVH via the addition
of myocardial contractile fibers in
parallel. The thickening of the LV
walls ↓ LV compliance, leading to
impaired diastolic filling and HF
w/ preserved EF. In response to ↓
CO, the kidneys activate the
RAAS, stimulating Na retention
and vasoconstriction that worsens
volume overload and can lead to
DHF.
Cardiovascular (CV)
Physiology (Phys) 4
15516
Hypertrophic
cardiomyopathy
HCM typically involves
interventricular septal
hypertrophy that obstructs LV
outflow and creates a systolic
murmur that ↓ in intensity w/
maneuvers that ↑ LV blood
volume (eg, hand grip, passive
leg elevation). HCM is Chx by ↑
LV muscle mass w/ a small LV
cavity, preserved EF, and
impaired LV relaxation leading to
diastolic dysfxn.
Cardiovascular (CV)
Physiology (Phys) 9
15526
Acute heart failure SV is the absolute volume of
blood ejected from the LV w/
each contraction and is calculated
by subtracting LV ESV from LV
EDV. EF is the relative volume of
blood ejected from the LV w/
each contraction; it is calculated
by dividing SV by LV EDV. CO,
the volume of blood ejected into
the aorta per unit time, is
estimated by multiplying SV by
HR.
Cardiovascular (CV)
Physiology (Phys) 7
15534
Chronic heart
failure
Cardiovascular (CV)
Physiology (Phys) 12
LHF leads to chronically ↑ pulm
venous and capillary pressures,
w/ resulting pulm oedema and
extravasation of RBCs into the
alveolar parenchyma. The Fe
from RBCs is taken up by
alveolar macrophages and stored
as hemosiderin, appearing as
brown pigment on
histopathology.