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Dr.

Abdul Majid SpPD-KKV

PATHOFISIOLOGI KARDIOVASKULAR

Dr.Abdul Majid SpPD-KKV

Lahir:

Rantau Prapat, 29 Juli 1945.

Pendidikan:
*Dokter umum : FK USU
*Spesialis Peny.Dalam: FK USU
*Konsultan Kardiovaskular
(Cardiologist):FK UI Jakarta.

Pekerjaan:

Bagian Fisiologi FK USU


Konsultan Peny.Dalam &
Jantung RS Permata Bunda
Medan
Alamat:

Jln KIWI Taman Kuswari Indah II/M37, Medan

Tel: 62-61

8469960; HP:08126040589

PATHOFISIOLOGI
SISTEM KARDIOVASKULAR
HIPERTENSI
PENYAKIT JANTUNG KORONER
KELAINAN KATUP JANTUNG
ARITMIA
GAGAL JANTUNG
SHOCK
DISFUNGSI ENDOTEL
DLL

THE
PATHOPHYSIOLOGY
OF HYPERTENSION

Dr.Abdul Majid
Bagian Fisiologi FK USU Medan

Hypertension practice

Guidelines
JNC 7
2003

W H O 1999

I S H 1999
2003 Canadian

ESC 2003

Recommendations
for the Management of
Hypertension

British Society of
Hypertension
2003/2004
Kaplan`s
Clinical
Hypertension
2002

Hypertension Syndrome

Its More Than Just Blood


Pressure
Decreased

Arterial
Compliance Endothelial
Obesity
Dysfunction
Abnormal
Abnormal
Glucose
Lipid
Metabolis
Metabolism
m
Hypertension
Accelerated
Neurohormona
Atherogenesi
l
s
Dysfunction
RenalLV Hypertrophy
Function
Bloodand Dysfunction
Abnormal
Clotting Changes
Insulin
Mechanism
Metabolism
Changes
Kannel WB. JAMA. 1996;275:1571-1576. Weber MA et al. J Hum Hypertens. 1991;5:417-423. Dzau
VJ et al. J Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5.

ESC 2003

ESH 2003 & JNC VII(2003)

ESH-ESC 2003
BP Classification

JNC 7
2003

BP

BP

Optimal

<120 / <80

<120/<80

Normal

120-129 / 80-84

120-129 /80-84

Prehypertension

High normal

130-139 / 85-89

130-139 / 85-89

Prehypertension

Grade 1
Hypertension (mild)

140-159 / 90-99

140-159 / 90-99

Stage 1
Hypertension

Grade 2
Hypertension
(moderate)
Grade 3
Hypertension
(severe)
Isolated Systolic
Hypertension

160-179 /100109

>160 / >100

JNC VII(2003)
Bp
Classification
Normal

Stage 2
Hypertension

> 180 / >110

> 140

< 90

Isolated Systolic
Hypertension

Types of hypertension
Essential Hypertension
hypertension with no apparent cause

Secondary Hypertension
hypertension of known cause

chronic renal diseases


Renovascular diseases
Oral contraceptive pills
Coarctation of the Aorta
Primary aldosteronism
Pheochromocytoma

2.5-5%
0.5-4%
0.2-1%
0.1-1%
0.1-0.5%
0.1-0.2%

90-95%

Risk Factors
Age
Gender (18- 70)
Race
Genetic factors
.Other:
obesity
high alcohol intake
high Na intake
abnormal renin values
high stress level
low birth weight
drugs

Patho-physiology of Hypertension
HTN develop gradually over a long period of time.
The development of HTN requires the adjustment of several
compensatory mechanisms over time.
Several hypothesis exists for the original pathogenesis of HTN:

Excess Na intake
Renal Na retention
Renal Angiotensin System (RAS)
Stress & sympathetic over activity
Peripheral resistance
cell membrane and endothelial dysfunction
Obesity
insulin resistance

Reduced
Excess Na Nephron
intake
Numbers

Stress

Genetic
Alterations Obesity

Endothelium
derived
factors

Decreased
Renal Na
Sympatheic RAS Cell-membrane
Hyper
filtration
retention
Over activity Excess alterations insulinemia
surface

Fluid
Volume

Venous
constriction

Preload

Functional
Contractibility
constriction

Blood pressure= Cardiac Output X Peripheral


HTN
and/orResistance

Structural
hypertrophy

Pathophysiology of blood
pressure changes
BLOOD
PRESSURE
CARDIAC
OUTPUT
BLOOD VOLUME

PERIPHERAL
RESISTANCE
FUNCTIONAL
VASOCONSTRICTION

CONTRACTILITY
Normal Remodeling
PULSE RATE

STRUCTURAL HYPERTROPHY

IMPACT OF
HYPERTENSION
ON
TARGET ORGANS

Complications of HTN
CNS

Cardiac

Renal

Stroke or TIA

Sequelae of
Hypertension
Heart diseases

Retinal

Retinopathy

Nephropathy,
Proteinuria, CrCl

Vascular

Peripheral arterial
Disease (atherosclerotic
plaque iliac,carotid,
femoral artery, aorta)

Renal Complications
Benign arteriolar
Nephrosclerosis
Malignant arteriolar
Nephrosclerosis
Chronic Renal
Failure

How does HT damage the


kidney?
Vasoconstriction of Decrease of
Imbalance
Atherosclerosis preglomerular vesselsthe number ofof afferent and efferent
nephrons
arteriolar tone

GLOMERULAR
HYPERPRESSURE

RENAL ISCHEMIA

Tubulo-interstitial
changes

Glomerular
changes

CNS Complications
Hypertensive
encephalopathy
Cerebral
hemorrhage
Ischemic stroke
TIAs

Development of Central Nervous System


Lesions due to Hypertension
Atherosclerosis

Small vessels
Charcot
Loss of
Hyaline Sclerosis microaneurysms Self-regulation

ISCHEMIA

Dementia

HEMORRHAGE

Stroke

EDEMA

Encephalopathy

Retinal complications
Hypertensive retinopathy

Venous
tapering
Increased
light reflexes
from
arterioles

Blurred
optic disc

Punctate
hard
exudate

Normal

hemorrhag
e

Vascular Complications
Artherioscelorosis
wall:lumen ratio
remodeling

Atherosclerosis
Plaque
Fibrous cap
necrotic center

Fibrinoid necrosis.
Aortic dissection.
Normal Remodeling

Cardiac Damage in
Hypertension

HT is the main risk factor for heart failure and


one of the main risk factors for ischemic
cardiomyopathy

CHF prevalence is increasing, whereas the


incidence of ischemic cardiomyopathy is
decreasing

Antihypertensive treatment reduces ischemic


heart disease risk by 16% at 10 years and up
to 25% after a longer period

Cardiac Sequelae of
Hypertension
Left Ventricle Hypertrophy

Arrhythmias

Heart failure

Coronary Heart Disease

Progression from hypertension to heart failure


Obesity
DM

LVH

Diastolic
dysfunction
CHF

Hypertension
Smoking
Dyslipidemia
DM
Normal LV
structure and function

MI

LV remodelling
Time
(decades)

Death

Systolic
dysfunction

Subclinical
LV dysfunction

Overt
heart failure

Time
(months)
Arch Intern Med 1996;156

PATHOFISIOLOGI

GAGAL JANTUNG
(Heart Failure)

Pathophysiologic mechanisms of hypertension.(2).

Oparil S et al. Ann Intern Med 2003;139:761-776

2003 by American College of Physicians

Heart Failure
a major public health problem and
its prevalence is rising, with a
projected 2- to 3-fold increase over
the next decade.
Heart failure is primarily a disease of
the elderly
6% to 10% of people older than 65
years have HF ,and 80% of patients
hospitalized with HF are more than
65 years old ..
HF is often associated with poor
outcome; the 5-year mortality rate is
50%. (despite advances in treatment).

Oxygen

Carbon dioxide

Heart 2000;84(Suppl I):i20-i22

Coronary
Thrombosis
Myocardial
Ischemia
Stroke CAD

Myocardial
Infarction

Silent
Angina
Hibernation

PVD

Atherosclerosis
LVH
End
stage
Risk factors
Heart
Hypertension, High Cholesterol, D M, Disease
Smoking, Platelets, fibrinogen

Arrhythmia
and Loss of
Muscle

Sudden
Death

Remodeling

Ventricular
Dilation

Congestive
Heart Failure

Chain of events leading to end stage heart disease

Kemampuan Pompa Jantung


( Cardiac Performance)
Kontraktilitas

Denyut jantung

Preload ( beban awal)


dipengaruhi oleh end diastolic
volume (EDV)

Afterload (beban susulan )


ditentukan oleh resistensi perifer

A Report of the American College of Cardiology/American


Heart Association Task Force on Practice Guidelines
Page last updated
03/04/2002

(Committee to Revise the 1995 Guidelines for the Evaluation and


Management of Heart Failure)

Heart failure is.


a complex clinical syndrome that can
result from any
structural or functional cardiac
disorder
that impairs the ability of the ventricle
to fill with or eject blood.

A Report of the American College of Cardiology/American Heart Association Task Force


on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and
Management of Heart Failure)

The cardinal manifestations of HF are :


dyspnea and fatigue, which may limit exercise tolerance,
fluid retention, which may lead to pulmonary congestion
and peripheral edema.

Because not all patients have volume overload at the time


of initial or subsequent evaluation, the term

"heart failure"

is preferred over the older term

"congestive heart failure."

Etiology of Heart Failure


Coronary artery
disease
Hypertension

Others:

Idiopathic cardiomyopathy
Myocarditis
Valvular heart disease
Familial
toxic, metabolic

200
180
160
140
120
100

120
110
100
90
80
70

Classification of Heart Failure


NYHA = New York Heart Association
NYHA Class I

No limitation. Ordinary physical exercise does not


cause fatigue, dyspnea, or palpitation

NYHA Class II Slight limitation of physical activity.


Comfortable at rest, but ordinary activity results in
fatigue, dyspnea, or palpitation
NYHA Class III Marked limitation of physical activity, but less than
ordinary activity results in symptom
NYHA Class IV Unable to carry any physical activity. Symptoms
of HF are present even at rest, with increased
discomfort upon any level of physical activity

Stage A
At high risk for
heart failure but
without
structural heart
disease or
symptoms of HF

ACC/AHA Guidelines 2002


for the Evaluation and Management of
Chronic Heart Failure in the Adult

Stage B
Structural heart
disease but without
symptoms of HF

Stages in the evolution of heart


failure and recommended therapy
by stage.
Stage C
Structural heart disease
with prior or current
symptoms of HF

Stage D
Refractory HF requiring
specialized interventions

Stage A
At high risk for
heart failure
but
without
structural
heart disease
or
symptoms of
HF
St
ru
disheactur
ea rt al
se

Stages in the evolution of heart failure


and recommended therapy by stage.

eg,Patients with:
Hypertension
Coronary artery disease
Diabetes mellitus
or
Patients
using cardiotoxin
with FHxCM

Stage B
Structural heart
disease but without
symptoms of HF

FHx CM indicates family history of


cardiomyopathy; MI, myocardial infarction; LV,
left ventricular; and IV, intravenous.

eg, Patients with:


previous MI
LV systolic dysfunction
asymptomatic valvular disease

Stage C
Structural heart
disease with prior or
current symptoms of HF

eg, Patients with:


known structural heart disease
shortness of breath and fatigue,
reduced exercise tolerance

Stage D
Refractory HF requiring
specialized interventions

eg ,Patients who have:


marked symptoms at rest despite
maximal medical therapy ( eg, those
who are recurrently hospitalized or
cannot be safely discharged from
the hospital without specialized
interventions)

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult
A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995
Guidelines for the Evaluation and Management of Heart Failure)

Mekanik kompensasi
Gagal Jantung

Mekanik kompensasi Gagal Jantung

Respon jantung terhadap beban yang meningkat:

Hipertophi
konsentrik
(dilatasi )
sel otot >

Serat otot
jantung
memanjang /
dilatasi
Frank
Starling law

Peningkatan
aktifitas
simpatis
&
neurohormo
nal

Neurohumoral Control of the Cardiovascular System


RAAS

Angiotensinogen

SNS

Aldosterone
Angiotensin I

NEP

ACE

Natriuresis

ANP

AT II

relaxation

Myocardial
hypertrophy
fbrosis

Cardiovascular System

constriction

Mekanik kompensasi Gagal Jantung

Pening
katan
aktifitas
simpatis
&
neuro
hormonal

* daya kontraksi serabut otot yang memanjang


tanpa penigkatan tekanan pengisian
*stimulasi Renin-Angiotensin-Aldosterone system
* H.R dan resistensi vaskular sistemik untuk
mempertahankan tekanan darah
*tonus vena
*ADH(vasopressin)
*Oleh adanya regangan & tekanan atrium kiri dan
kanan, pelepasan Atrial Natriuretic factor
natriuresis dan diuresis.

Heart Failure

Hemodynamic
effect
Cardiac output

Pre Load

Sympathetic activity

Na& Fluid
retention

Hypo Renal
Perfusion

Reflex
Arteriolar
vasocons
triction

After Load

SVR

Neurohormonal hyperactivity

Renin, Angiotensin, Aldosterone, Vasopressin ,


ANP , BNP , Nor Epinephrine

Ventricular Failure

_
Cardiac Output

Systemic
Vascular
Resistance

Arterial
Pressure

Symphatetic
Angiotensin II
Aldosterone
Vasopressin

_
-

Atrial
Natriuretic
Peptide

Blood
Volume
Venous
pressure
Venous
Tone

Pulmonary
Edema
Systemic
Edema

Mekanik kompensasi berlebihan:

Hipertropi jantung

*Retensi Na & H2O >>

Tekanan atrium

* resistensi vaskular sistemik

Dilatasi ventrikel
Peningkatan daya kontraksi

Beban kerja fungsi tidak dapat dipertahankan


secara adekuat
Dekompensasi ( Gagal Jantung )

Gejala gejala Gagal Jantung


Sesak nafas bila aktifitas fisik
Mudah capek
Denyut jantung cepat
Kedua tungkai bengkak
Timbunan cairan ditubuh
Batuk-batuk ( malam hari)
dll

Jenis-jenis Gagal Jantung (Heart Failure)

Forward vs Backward Heart Failure

Gagal jantung kanan vs jantung kiri


Gagal jantung akut vs
Low output

vs

kronis

High output failure

Gagal jantung sistolik

vs

diastolik

Gagal Jantung Diastolik

Definisi
Gagal Jantung yang disebabkan oleh meningkatnya
resistensi terhadap pengisian pada satu atau kedua
ventrikel
EF NORMAL ( > 40 %)

Common etiology:

CAD

Hypertension

EDV 175.6 ml, EF 37%

EDV 70 ml, EF 65%

Diastolic Heart Failure

Systolic Heart Failure

Common etiology:

Faktor Presipitasi Gagal Jantung


Kardiak

:Aritmia , MCI.

Non kardiak : anemia, emboli paru,

pneumonia, tirotoksikosis, asupan


garam>>,penghentian obat, penggunaan cairan
parenteral yang cepat atau berlebihan, obat
NSAID, obat steroid, demam .

Kehamilan, dll

Acute Coronary Syndromes


Acute

(
A
C
S
)
Coronary Ischemic
Syndromes

A Major Medical Problem

UNSTABLE ANGINA & NONST-SEGMENT


ELEVATION MYOCARDIAL INFARCTION

2002

ACC/AHA GUIDELINES
Eugene Braunwald, MD, Chair

Feb.2001 British Cardiac


Society

Pathophysiology

Acute Coronary
Syndrome
(ACS)

Dr Abdul Majid SpPD-KKV

Heart
attack
Acute Coronary Syndrome ???

Acute Coronary Syndrome


Pasien dengan spektrum klinis rasa tidak enak didada
atau gejala lainnya yang disebabkan oleh iskemia miokard

The spectrum of clinical conditions ranging


from:

Unstable
angina

Non-Q wave
MI (NSTEMI)

Q-wave MI
(STEMI)

(UAP)

characterized by
the common pathophysiology of
a disrupted atheroslerotic plaque

ACS: physiopathology

Plaque Rupture Leads to Thrombus Formation


Unstable Plaque

Thin Fibrous Cap


Lipid Core

Ruptured Plaque

Thrombu
s

Inflammatory
Cells

Few
SMCs
Activated
Macropha
ges

Plaque Rupture Leads to Thrombus Formation

Yeghiazarians Y et al. N Engl J Med. 2000;342:101-114.

Role of Platelets in Thrombus


Formation
in Acute Ischemic Events

Lipid
Core

Atherosclerotic
Vessel

Plaque
Rupture

Platelet Adhesion,
Activation, and
Aggregation

Thrombus
Formation

Vessel wall injury Plaque rupture


Exposure of subendothelial collagen and
other platelet-adhering ligands

Schafer AI. Am J Med. 1996;101:199209.

Thrombotic
Occlusion

MI
Stroke
Vascular
Death

a cross-section of the coronary artery. Most of its wall is


filled with smooth muscle cells that can contract and relax.

Nitroglycerin dilates constricted arteries.

atherosclerotic plaque( consists of cholesterol, inflammatory cells,


and fibrosis, and it reduces the space for blood flow in the artery.)

A spasm can suddenly develop in an atherosclerotic


coronary artery ( angina pectoris)

The anterior surface of the heart


demonstrates an opened left anterior
descending coronary artery. Within the
lumen of the coronary can be seen a dark
red recent coronary thrombosis. The dull
red color to the myocardium as seen
below the glistening epicardium to the
lower right of the thrombus is consistent
with underlying myocardial infarction.

At high magnification, the dark red


thrombus is apparent in the lumen of
the coronary. The yellow tan plaques
of atheroma narrow this coronary
significantly, and the thrombus
occludes it completely.

Koroner normal
Pasokan seimbang dengan kebutuhan
(aliran darah koroner)

(kebutuhan miokard)

PJK Pasokan ,
tetap

kebutuhan

Pasokan tetap, kebutuhan

Risk Factors
of
ACS

Assessment of
cardiovascular risk
Predisposing Risk Factors

Major independent Risk Factors


Cigarette smoking
Elevated Blood
Pressure
Elevated serum LDL
cholesterol
Low serum HDL
cholesterol
Diabetes Mellitus
Advancing Age
Risk parallels Endothelial
Dysfunction !! !!
Grundy et al, J Am Coll Cardiol 1999;34:1348-59

Obesity
Abdominal Obesity
Physical inactivity
Family history of premature CHD
Ethnic characteristics
Psychosocial factors

Conditional risk factors


Elevated serum triglycerides
Small LDL particles
Elevated serum homocysteine
Elevated serum lipoprotein(a)
Prothrombotic factors
(eg, fibrinogen)
Inflammatory markers
(eg, C-reactive protein)

Endothelial Dysfunction and


Cardiovascular Disease
Vasospasm
Coronary, Cerebral
Reocclusion

Heart Failure
Thrombosis
Coagulopathy
Diabetic
Diabetic
Angiopathy
Angiopathy

Hypertension
Reperfusion
Injury

Endothelial
Dysfunction

Peripheral Artery
Disease

Hyperlipidemia

Inflammatory
Disease

Immune Reaction
Atherosclerosis

Adapted from Rubanyi GM: J Cardiovasc Pharmacol.1993;22(suppl 4) S1-S14

Atherosclerosis
Carotid
Arteries
Coronary
Arteries

Peripheral
Vasculature

Stroke

Heart Attack
Angina

Intermittent
Claudication

Patofisiologi SKA
Agregasi trombosit,
akumulasi lipid & makrofag
Plak stabil

Plak tak
stabil
Injury &
disfungsi endotel

Hipertensi
Merokok
DM
Dislipidemia
Zat vasoaktif
dll
Disfungsi endotel

disrupsi
Trombosis akut
APTS
Oklusi koroner
IMA

Platelet & thrombin


dependent vasoconstriction

Vasokonstriksi

Atherosclerosis: A Progressive Process


Normal

Fatty
Streak

Fibrous
Plaque

Occlusive
Atherosclerotic
Plaque

Plaque
Rupture/
Fissure &
Thrombosis

Unstable
Angina

MI

Coronary
Death

Stroke

Effort Angina
Claudication

Clinically Silent

Increasing Age

Courtesy of P Ganz.

Critical Leg
Ischemia

UA/NSTEMI
PATHOGENESIS (NONEXCLUSIVE)
Nonocclusive thrombus on
pre-existing plaque

CAUSES OF UA/NSTEMI
Mechanical
Obstruction

Thrombosis

Dynamic
Obstruction

Dynamic obstruction
(coronary spasm or
vasoconstriction)

MVO2

Inflammation/
Infection
Mechanical
Obstruction

Thrombosis

Progressive mechanical
obstruction
Inflammation and/or
infection
Secondary UA

.
MVO2

Dynamic
Obstruction

Inflammation/
Infection

Braunwald Circulation 98:2219, 1998

Worldwide Statistics
Each year:
> 4 million patients are admitted with
unstable angina and acute MI
> 900,000 patients undergo PTCA
with or without stent

CABG

Traditional Coronary Artery Bypass


Grafts. One vein graft is sutured to the
aorta, then to the LAD .

(Coronary Artery Bypass Grafts)

Spectrum of Acute coronary syndromes


AcuteCoronary
CoronarySyndrome
Syndrome
Acute
NoST
STElevation
Elevation
No

STElevation
Elevation
ST

Non ST Elevation MI

UnstableAngina
Angina
Unstable

Myocardial Infarction
Infarction
Myocardial
NonQw
QwMI
MI
QwMI
MI
Non
Qw
(NSTEMI)
(NSTEMI)

Braunwald E et al. J Am Coll Cardiol 2000;36:9701062.

(STEMI)
(STEMI)

Diagnosis ACS

Chest pain
( typical)

ECG
changes

Cardiac
serum
marker

Myocardial Ischemia
silent ischemia

Spectrum

of
presentation

exertion-induced
angina
unstable angina
acute myocardial
infarction

Ischemic Heart Disease

evaluation
Based on the patients
history / physical exam
ECG

Patients are categorized into :


non-cardiac chest pain

cardiac chest pain


Stable angina
Unstable angina
myocardial infarction

UA/NSTEMI
EMERGENCY ROOM TRIAGE

Chest pain or severe epigastric pain, typical of myocardial


ischemia or MI:

Substernal compression or crushing chest pain


Pressure, tightness, heaviness, cramping, aching

sensation
Unexplained indigestion, belching, epigastric pain
Radiating pain to neck, jaw, shoulders, back or to
one or both arms

Associated dyspnea, nausea and/or vomiting, diaphoresis


IF THESE SYMPTOMS ARE PRESENT, OBTAIN STAT ECG

Ischemic chest pain

FEATURES NOT CHARACTERISTIC


OF MYOCARDIAL ISCHEMIA

Pleuritic pain (i.e., sharp or knife-like pain


brought on by respiratory movements or cough)
Primary or sole location of discomfort in the
middle or lower abdominal region
Pain that may be localized at the tip of 1 finger,
particularly over the LV apex
Pain reproduced with movement or palpation of
the chest wall or arms
Very brief episodes of pain that last a few
seconds or less
Pain that radiates into the lower extremities

UA/NSTEMI
THREE PRINCIPAL PRESENTATIONS
Rest Angina*

Angina occurring at rest and prolonged,


usually > 20 minutes, occurring within 1
week of presentation

New-onset Angina New-onset angina of at least CCS Class III


severity ( marked limitation of ordinary
physical activity) severity with onset within 2
mo of initial presentation

Increasing Angina

Previously diagnosed angina that has


become distinctly more frequent, longer in
duration, or lower in threshold (i.e., increased
by > 1 CCS) class to at least CCS Class III
severity.

* Pts with NSTEMI usually present with angina at rest.

Braunwald Circulation 80:410; 1989

ECG changes in Acute Coronary Syndrome


ST depression with/ without T inverted, Q wave (-)

UAP
ST depression,

deep T inverted

Non Q MCI
(NSTEMI)
hyper acute T (0-1 hrs),

ST elevation (hours),

Q wave
MCI(STEMI)
Q wave (8-48 hrs),

T inverted (1-2 days)

Unstable Angina : Likelihood of CAD

Previous history of CAD


presence of risk factors
older age
ST-T wave ischemic ECG changes
Chest pain (-)

Chest pain (+)

Agency for Health Care Policy Research - 1994

Non-Q-Wave MI:

diagnosis
Prolonged chest pain
Associated symptoms
from the autonomic
nervous system
nausea, vomiting,
diaphoresis

Persistent ST-segment
depression after
resolution of chest pain

Clues to

Q-Wave MI:
Prolonged chest pain
Associated symptoms
from the autonomic
nervous system
nausea, vomiting,
diaphoresis

ST-segment elevation/
Q wave

Clues to diagnosis

MCI non Q
(Non ST
Elevation MI)

Subendokard

Subepikard

ST depression
T inverted
Q wave (-)

MCI Q wave
(ST Elevation MI)

ST elevation
T inverted
Q wave(+)

II

III

aVR

aVL

aVF

Cardiac serum marker in Acute Myocardial Infarction

Troponin as Predictor of Ischemic Events


Death or MI at 30 days (n = 773)

NEJM 1997;337:1648-1653

FEATURE

HIGH OR INTERMEDIATE
LIKELIHOOD THAT
UA/NSTEMI IS CAUSED BY
HIGH LIKELIHOOD
INTERMEDIATE LIKELIHOOD
OBSTRUCTIVE
CAD
Absence of high-likelihood features
and presence of any of the following:

History

Examination

Chest or left arm


pain reproducing
prior documented
angina. Known
history of CAD,
including MI

Chest or left arm


pain or
discomfort
Age > 70
Male sex
Diabetes mellitus

Transient MR,
hypotension,
diaphoresis,
pulmonary edema,

Extracardiac
vascular disease

HIGH OR INTERMEDIATE LIKELIHOOD THAT


UA/NSTEMI IS CAUSED BY OBSTRUCTIVE CAD
FEATURE

HIGH LIKELIHOOD

INTERMEDIATE LIKELIHOOD
Absence of high-likelihood features
and presence of any of the following:

ECG

New transient STsegment deviation or


T-wave inversion
(0.2 mV) with symptoms

Fixed Q waves
Abnormal ST segments
or T waves not
documented to be new

Cardiac
markers

Elevated cardiac Tnl, TnT,


or CK-MB

Normal

Acute Coronary
Syndrome
Ischemic Discomfort
Unstable Symptoms

No ST-segment
elevation

Unstable
angina

History
Physical Exam

ST-segment
elevation

Non-Q
AMI

Q-Wave
AMI

ECG

Acute
Reperfusion

Plaque Rupture with Thrombosis


Thrombus

Fibrous cap

1 mm
Lipid core
Illustration courtesy of Frederick J. Schoen, M.D., Ph.D.

Acute Coronary Syndrome


Process of resolution
spontaneous thrombolysis
vasoconstriction resolution
presence of collateral
circulation
Delayed or absence of resolution
may lead to
non-Q-wave or Q-wave myocardial
infarction

To exclude an acute coronary syndrome:


If at 12 h after onset of symptoms
Symptoms have not recured
ECG is normal
CK-MB is normal
Troponin is normal

The patient can be mobilized and


discharge
Their risk should be assessed with a
stress test
Feb.2001 British Cardiac Society

Suspected Cardiac
Pain
ECG
No ECG
ST

ECG ST
Or LBBB
Acute

MI

Normal ECG,

ECG ischemic or

CK-MB,& cTn

CK-MB or cTn

Suspected
ACS

Feb.2001 British Cardiac Society

Confirmed
ACS

Let it
beat!

Pathophysiology
arrhythmias
. ECG Rhythm Abnormalities
Topics for Study:

1. Introduction to rhythm analysis


2. Supraventricular arrhythmias
3. Ventricular arrhythmias

Electrocardiogram (ECG; EKG)


the chart recording of the electrical activity of the heart as measured from the body surface potentials
Systole period of myocardial contraction
Diastole period of cardiac muscle relaxation

P wave corresponds to atrial depolarization


PR interval a measure of the conduction time required for an impulse to be conducted from the atria to the ventric
QRS complex represents depolarization of the ventricles
S-T segment interval between ventricular depolarization and repolarization
T wave reflects ventricular repolarization

V. ECG Rhythm Abnormalities


Topics for Study:
1. Introduction to rhythm analysis
2. Supraventricular arrhythmias

Premature atrial complexes


Premature junctional complexes
Atrial fibrillation
Atrial flutter
Ectopic atrial tachycardia and rythm
Multifocal atrial tachycardia
Paroxysmal supraventricular tachycardia
Junctional rhythms and tachycardias

V. ECG Rhythm Abnormalities


Topics for Study:
3. Ventricular arrhythmias

Premature ventricular complexes (PVCs)


Aberrancy vs. ventricular ectopy
Ventricular tachycardia
Differential diagnosis of wide QRS tachycardias
Accelerated ventricular rhythms
Idioventricular rhythm
Ventricular parasystole

Lesson V (cont) Supraventricular Arrhythmias

1.Premature atrial complexes


2.Premature junctional complexes
3.Atrial fibrillation
4.Atrial flutter
5.Ectopic atrial tachycardia and rhythm
6.Multifocal atrial tachycardia
7.Paroxysmal supraventricular tachycardia
8.Junctional rhythms and tachycardias

Supraventricular Arrhythmias

1. Premature atrial complexes

Occur as single or repetitive events and have unifocal or


multifocal origins.

The ectopic P wave (called P') is often hidden in the ST-T


wave of the preceding beat. (Dr. Marriott, master ECG
teacher and author, likes to say: "Cherchez le P on let T"
which in French means: "Search for the P on the T wave",
but it's more sexy in French!)

The P'R interval is normal or prolonged because the AV


junction is often partially refractory when the premature
impulse enters it.

The pause after a PAC is usually incomplete; i.e., the


PAC usually enters the sinus node and resets its timing,
causing the next sinus P to appear earlier than expected.
(PVCs, on the other hand, are usually followed by a
complete pause because the PVC does not usually
perturb the sinus node; see ECG below.)

3. Atrial Fibrillation (A-fib)

4. Atrial Flutter (A-flutter):

Regular atrial activity with a "clean" saw-tooth appearance in leads II, III, aVF,
and usually discrete 'P' waves in lead V1. The atrial rate is usually about 300/min,
but may be as slow as 150-200/min or as fast as 400-450/min.

8. Junctional Rhythms and Tachycardias

Junctional Escape Rhythm: This is a sequence of 3 or more junctional


escapes occurring by default at a rate of 40-60 bpm. There may be AV
dissociation or the atria may be captured retrogradely by the junctional
pacemaker. In the ECG example below the retrograde P waves are not seen
and must be hidden in the QRS's; the significant "Q" wave with ST elevation
in the bottom strip suggests an acute MI.

Lesson V (cont ) Ventricular arrhythmias


1.Premature ventricular complexes (PVCs)
2.Aberrancy vs. ventricular ectopy
3.Ventricular tachycardia
4.Differential diagnosis of wide QRS
tachycardias
5.Accelerated ventricular rhythms
6.Idioventricular rhythm
7.Ventricular parasystole

1. Premature Ventricular Complexes (PVCs)

PVCs may be unifocal (see above), multifocal (see below) or multiformed. Multifocal PVCs
have different sites of origin, which means their coupling intervals (measured from the previous
QRS complexes) are usually different. Multiformed PVCs usually have the same coupling
intervals (because they originate in the same ectopic site but their conduction through the
ventricles differ. Multiformed PVCs are common in digitalis intoxication.

PVCs may occur as isolated single events or as couplets, triplets, and


salvos (4-6 PVCs in a row), also called brief ventricular tachycardias .

PVCs may occur early in the cycle (R-on-T phenomenon), after the T wave
(as seen above), or late in the cycle - often fusing with the next QRS (fusion
beat). R-on-T PVCs may be especially dangerous in an acute ischemic
situation, because the ventricles may be more vulnerable to ventricular
tachycardia or fibrillation. Examples are seen below.

In the above example, "late" (end-diastolic) PVCs are illustrated with varying degrees of fusion. For
fusion to occur the sinus P wave must have made it to the ventricles to start the activation sequence,
but before ventricular activation is completed the "late" PVC occurs. The resultant QRS looks a bit
like the normal QRS, and a bit like the PVC; i.e., a fusion QRS.

3. Atrio-Ventricular (AV) Block


Possible sites of AV block:
AV node (most common)
His bundle (uncommon)
Bundle branch and fascicular divisions (in presence of already
existing complete bundle branch block)

1st Degree AV Block: PR interval > 0.20 sec; all P waves conduct to the
ventricles.

Type I (Wenckebach) AV block (note the RR intervals in ms duration):


Type I AV block is almost always located in the
AV node, which means that the QRS duration is
usually narrow, unless there is preexisting
bundle branch disease.

Type II (Mobitz) AV block(note there are two consecutive constant PR intervals


before the blocked P wave):

Type II AV block is almost always located in the bundle branches, which means that the
QRS duration is wide indicating complete block of one bundle; the nonconducted P wave is blocked in the
other bundle. In Type II block several consecutive P waves may be blocked as illustrated below:

Complete (3rd Degree) AV Block


Usually see complete AV dissociation because the atria and
ventricles are each controlled by separate pacemakers.

Narrow QRS rhythm suggests a junctional escape focus for the


ventricles with block above the pacemaker focus, usually in the AV

node.

Wide QRS rhythm suggests a ventricular escape focus (i.e.,


idioventricular rhythm). This is seen in ECG 'A' below; ECG 'B'
shows the
treatment for 3rd degree AV block; i.e., a ventricular pacemaker. The location of
the block may be in the AV junction or
bilaterally in the bundle branches.

Left Bundle Branch Block (LBBB)


"Complete" LBBB" has a QRS duration >0.12s
Close examination of QRS complex in various leads reveals that the
terminal forces (i.e., 2nd half of QRS) are oriented leftward and posteriorly
because the left ventricle is depolarized after the right ventricle.

Terminal S waves in lead V1 indicating late posterior forces

Terminal R waves in lead I, aVL, V6 indicating late leftward


forces; usually broad, monophasic R waves are seen in these leads
as illustrated in the ECG below; in addition, poor R progression from
V1 to V3 is common.

Wolff-Parkinson-White Preexcitation

Pathophysiologi
Endothelial dysfunction:

Dr Abdul Majid SpPD-KKV


Dept. of Physiology FK USU
Consultant Internist and Cardiologist Permata Bunda Hospital
Medan

Ten to 20 years ago .


the cardiovascular was thought to be
controlled by
circulating factors such as
the renin- angiotensin system
and
the sympathetic nervous system
which were able to regulate the
heart, kidney , and the blood vessels

Heart 2000;84(Suppl I):i20-i22

More recently, however, it has become


evident that the blood vessels itself plays an
important role that involves many factors
including
nitric oxide, which is vasodilator,
and endothelin, a vasoconstrictor.
In fact, the endothelium is altered
morphologically as a result of coronary artery
disease.
Heart 2000;84(Suppl I):i20-i22

References

Journal of Cardiovascular Pharmacology


22(Suppl, 4);SI-S14@1993 Raven Press, Ltd, New York

The Role of Endothelium in Cardiovascular


Homeostasis and Disease
Gabor M.Rubanyi

Cardivascular Research, Berlex Bioscience, Richmond. California, USA

OCTOBER 1997

SEPTEMBER 2000 VOLUME 84 SUPPLEMENT I

VOLUME 18 No 10
PP 1530-1535

The
Endotheliu
m in
Clinical
Practice
edited by

Source and Target of Novel Therapies

THE ENDOTHELIUM:
A PIVOTAL ROLE IN
HEALTH AND
CARDIOVASCULAR
DISEASE

DO ACE
INHIBITORS
MODULATE
ATHEROSCLEROSIS?

Gabor M.Rubanyi
Victor J.Dzau

European Heart
Journal
Journal of the European
Society of Cardiology

Heart
Evolving Strategies in
Cardiovascular Care:
The Renin-Angiotensin
System and the Future

C.M. BOULANGER P.M.


VANHOUTTE
British Cardiac Society

The Relevance of Tissue


Angiotensin- Converting Enzymes:
Manifestations in Mechanistic and Endpoint Data.
Victor J.Dzau,Kenneth Bernstein, David Celermajer , et al.
Am J Cardiol 2001;88(suppl):I L-20L

BMJ

Clinical Assessment of Endothelial Function


Hiroaki Shimokawa, M.D., Ph.D.

Oxygen

Carbon dioxide

Blood vessels
All have endothelial lining

High power view of endothelial cells lining a small


blood vessel cut in cross-section. (You see just
the nuclei - the cytoplasm between them is
extremely flat.) Endothelium = the simple
squamous epithelium lining blood vessels.

Low power view of larger vessels, showing


endothelial nuclei lining the lumen. The
yellowish cells filling each vessel's lumen are
blood cells.

The Nobel Prize in Physiology or Medicine 1998


The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, has awarded the
Nobel Prize in Physiology or Medicine for 1998 to Robert F Furchgott, Louis J Ignarro and
Ferid Murad for their discoveries concerning "the nitric oxide as a signalling molecule in the
cardiovascular system".

Robert F Furchgott, born 1916


Dept. of Pharmacology,
SUNY Health Science Center
New YorkLouis

J Ignarro, born 1941


Dept. of Molecular and
Medical Pharmacology
UCLA School of Medicine
Los AngelesFerid

Murad, born 1936


Dept. of Integrative Biology
Pharmacology and Physiology
University of Texas Medical School, Houston

A New Principle
Nitric Oxide, NO, is a short-lived, endogenously produced gas that acts as a signalling
molecule in the body. Signal transmission by a gas, produced by one cell, which penetrates
membranes and regulates the function of other cells is an entirely new principle for signalling
in the human organism.

Contents
:Introduction Furchgott's sandwich Ignarro's spectral analyis Murad's enzyme activation Nitroglycerine, a 100 year old explosive and heart
medicine NO has many Clinical Applications
These pages are based on material from the 1998 Physiology or Medicine Nobel Poster.
Credits and references for the poster

ENDOTHELIAL CELLS(ARE)MORE THAN


A SHEAT OF NUCLEATED CELLPHANE
LORD FLOREY,1966

Physiolo
gy
of the
Endothel

The Endothelium : A Living Organ


In a 70 kg man,
the total of
endothelial cells
is 1 trillion

The
endothelium
is the largest
organ in
the body

In a 70 kg man,
its total surface
area is 6 tennis
courts
The Healthy Endothelium

In a 70 kg man,
its total weight is
1,800 g (> the
liver, -- 5 hearts

The Endothelium and Surrounding


Elements
Blood cells
Coagulation elements

LDL-cholesterol

Endothelium
Subendothelial
matrix

Smooth muscle

The
endothelium
is not only a selective barrier ,
it also has metabolic and
secretory activity.
In 1980 , it was discovered that
the endothelium released
a)Vasodilator substance(s)
EDRF (endothelium derived
relaxing factor)
b)Vasoconstrictor substances

Endothelial cells
Aggregating platelets
Bradykinin
Ach Histamine AVP
M2

H2

VP1

Smooth muscle cells

A,
NA

AA

B2

EDRF(s)
Relaxation

ADP

5-HT

P2

5-HTI

Thrombin Endothelin
T

ET

Vascular
Endothelium

a cross-section of the coronary artery. Most of


its wall is filled with smooth muscle cells that
can contract and relax.

Recognized
Recognizedas
asaamajor
majorregulator
regulatorofof

vasculartone
toneand
andhemostasis
hemostasis
vascular
Provides
Providesaasmooth,
smooth,non-thrombogenic
non-thrombogenic

surfaceand
andaapermeability
permeabilitybarrier
barrier
surface
Synthesizes
Synthesizesand
andreleases
releasesaanumber
numberofof

vasoactivesubstances
substancesthat
thatcontrol
control
vasoactive
relaxationand
andcontraction,
contraction,
relaxation
thrombogenesisand
andfibrinolysis,
fibrinolysis,and
and
thrombogenesis
plateletactivation
activationand
andinhibition
inhibition
platelet
Contributes
Contributestotoblood
bloodpressure
pressurecontrol,
control,

bloodflow,
flow,vessel
vesselpatency
patency
blood
Pepine, C., et. al., Vascular Health as as Therapeutic Target in Cardiovascular Disease, Vascular Biology
Working Group, University of Florida, 1998.

Substances Released by Endothelium


Vasoactive Substances
Vasoconstrictors

Vasodilators
Nitric

oxide (N0) / EDRF

EDHF
Prostacycline

Endothelin
Angiotensin

(PGI2)

Bradykinin
Acetylcholine,

serotonine, histamine,
substance P, etc

II

Thomboxane

A2,

Acetylcholine,
arichdonic acid,
prostaglandin H2, etc

Substances Released by Endothelium


Growth Mediators/Modulators
Growth promototrs : VEGF, FGF
Growth inhibitors

: tGFbeta, NO, prostacycline

Hemostasis and Thrombosis


Anti-thrombogenic factors: t-PA (tissue plasminogen activator),
Thrombogenic factors:

TM (thrombomodulin), heparin sulfate


VWF ( von Willebrand factor),
PA-I (plasminogen activator inhibitor),
adhesive glycoproteins

Inflammatory modulators /
mediators
Adhesion molecules: ELAM, ICAM
Antigens : MHC-II
Luscher, T., Barton, M., Biology of the Endothelium, Clinical Cardiology, vol. 20 (Suppl. II0, II-3 -II-10 (1997).

Cells

Blood

P MNS
Monocytes
Platelets

Endothelium

Physical Forces Vasoactive Substances


Shear Stress
Pressure

Peptides (thrombin, SP, VP)


Kinins(Bk)
Amines ( 5 HT )
Nucleotides ( ATP, ADP )
AA metabolites ( LTC 4 )

Endothelium Derived

Factors
Vascular
Proliferation
Smooth Muscle

Relaxation

Contraction

Modulation of the tone and structure of vascular smooth muscle by the vascular
endothelium.
The endothelial cell has the ability to sensechanges in hemodynamic (physical) forces, and
respond to vasoactive substances (circulating or locally produced), and mediators released from blood cells (e.g.
polymorphonuclear neutrophils,PMNs )and platelets. These stimuli then trigger the synthesis/ release of biologycally active
substances from the endothelium (endothelium-derived ( vasoactive ) factors) that modulate the tone (relaxation or
contraction) and structure of underlying vascular smooth muscle. By virtue of these recently discovered properties, the
vascular endothelium contributes to cardiovascular homeostasis in a significant way. SP, substance P, VP, vasopressin, Bk,
bradykinin, 5-HT, serotonin, ATP, adenosine triphosphat, ADP, adenosine diphosphate, LCT 4, leukotriene C4..

Adapted from Rubanyi GM: J Cardiovasc Pharmacol.1993;22(suppl 4) S

Endothelium derived mediators


Small Molecules :
Histamine
Free Radicals
EDRF ( NO, R NO )
Lipids :
Prostaglandin ( PGL 2 )
Leukotrienes
PAF

Proteins :
Endothelin ( ET 1 )
Growth Factors (PDGF)
Adhesion Molecules ( ELAM, ICAM, VCAM )
Matrix Proteins ( Heparine SO 4 )
Coagulation Factors( TF, tPA, PAI, TM, VWF )
Antigens ( MHC III )
Enzymes ( ACE )
Receptors

Biologycally active substances produced by the endothelial cell, which contribute to the physiologic and pathophyisiologic
functions of the vascular endothelium. EDRF, endothelium-derived relaxing factor; PGI 2, prostacyclin; NO, notric oxide; RNO, nitroso compound; PDGF, platelet-derived growth factor; PAF, platelet-activating factor; ET-1, endothelin 1; ELAM,
endothelial leukocyte adhesion molecule; ICAM,intrcellular adhesion molecule ; VCAM, vascular adhesion molecule TF,
tissue factor; t-PA, tissue plasminogen activator inhibitor; TM, thrombomodulin; VWF, von Willebrand factor; MHC-II, major
histocompatibility antigen II; ACE, angiotensin-converting enzyme.
Adapted from Rubanyi GM: J Cardiovasc Pharmacol.1993;22(suppl 4)
S1-S14

Permeability
Lipid
Transport
Vascular
Tone/Structure

Metabolic
Activity

Thrombosis
Hemostasis

Immune
Respons

Angiogenesis

Inflammation

Tumor
growth/metastasis
Some of the important physiologic and pathophysiologic functions
of the vascular endothelium.
Adapted from Rubanyi GM: J Cardiovasc Pharmacol.1993;22(suppl 4) S1-S14

Vasoactive Substances
Effects of Endothelin
Effects of NO
Vasodilator (via relaxation of
smooth muscle cells)
Growth inhibitor (via actions
on smooth muscle cells and
endothelial and mononuclear
cells)

Inhibitor of platelet
adherence/aggregation
Inhibitor of
endothelial/leukocyte
interactions

Pepine, C., et. al., Vascular Health as as Therapeutic Target in


Cardiovascular Disease, Vascular Biology Working Group,
University of Florida, 1998.

Powerful vasoconstriction
Release from endothelium
stimulated by Ang II

Effects of Bradykinin
Activates L-arginine-NO
pathway, promoting dilation
and inhibiting smooth muscle
cell proliferation
Activates release of
prostacyclin and EDHF,
inhibiting platelet
adherence/aggregation and
VSM contraction
Induces increase in t-PA
activity, promoting

fibrinolysis

B2
Endothelial
cell

L-citruline

L-Arg

NO-synthase

Nitric Oxide
(NO) Synthesis

NO
NO

Smooth
muscle
cell

NO

Peripheral

Renin Secretion

vasoconstriction

Renal

resistance

Glomerulo-tubular
Feedback

NO

Sodium

Reabsorption

Pressurenatriuresis

Endothelial health: A balancing act

Angiotensin II

Nitric Oxide

Endothelial Function Balance


Maintenance Vascular
Health

Vasodilation
Antiproliferatio
n
Antithrombotic
Antioxidant
Antiinflammatory

Vasoconstriction
Proliferation
Thrombotic
Pro-oxidant
Pro-inflammatory

Angiotensin I

Bradykinin
(active)
Inactive
peptide

Angiotensin II
A

A
Converting
enzyme

Endothelial cells

5-Hydroxytryptamine
Norepinephrine
Inactive metabolites

B
MAO

ATII

COMT

Basal membrane

Figure:
The handling of bioactive substances by the endothelium
A. Substances such as Angiotensin I and Bradykinin are transformed by converting enzyme located on the endothelial cell
membrane with resulting formation of active and inactive components, respectively.
B. Substances such as Norepinephrine and 5-Hydroxytryptamine (serotonin) are actively taken up and degraded
enzymatically by MAO and catechol-O-methyltransferase(COMT)
CM Boulanger, PM Vanhoutte: The Endothelium, 1994

Angiotensin I

Angiotensin II
AT
Renin

Prepro ET

Big ET

ACE
ECE

Endothelin I

AI

Contraction

AT1

Inactive
products

ACE

B2
L-Arginine

NOS2

Cyg

ATII

ATG

Angiotensin II

ETA

Bradykinin
(active)

NO

cGMP

AA

PGI2

cAMP

Relaxation

Figure: The endothelium plays an important role in the control of the vascular system.
Luscher TF, Heart 2000:84(Suppl I): i20-i22

Endothelial
dysfunction

The Endothelium

Endothelial Dysfunction
Any Alteration in normal endothelial

function
Results in imbalance between :
This scanning electron micrograph of coronary
artery endothelium. illustrates the fragility of
the endothelial monolayer. A few intact
endothelial cells can be seen in the upper left
corner, but the remainder of the vessel wall is
denuded of endothelium due to mechanical
injury by catheter manipulation. This results in
exposure of underlying smooth muscle and
connective tissue as well as platelet
aggregation.

- relaxing and contracting factors.


- anticoagulant and procoagulant
properties
- growth-inhibiting and promoting
factors

Oxidative stress
Angiotensin II

Nitric Oxide
Activity
Redox state : normal oxidative metabolism in arterial wall
( balanced superoxide anion and NO )
Oxidative stress : superoxide anion production and
breakdown of NO stimulate adhesion molecule expression and
promote leukocyte adhesion to endothelium, leading to
inflammatory response

Unifying model :Endothelial Dysfunction to Cardiovascular Disease


Hypoxia/ ischemia/
reperfusion
Hyperlipidemia Hypertension

Risk factors

DM

Smoking

Oxidative stress

Endothelial Dysfunction
NO . Local mediators . Tissue ACE leading to Angiotensin II
PAI-I

Thrombosis
Thrombosis

VCAM
ICAM cytokines

Endothelin

Inflammation Vasoconstriction
Vasoconstriction
Inflammation

Growth
factors marks

Vascularlesion
lesion
Vascular
andremodeling
remodeling
and

Proteolysis

Plaquerupture
rupture
Plaque

Clinical Sequelae
Gibbons GH, Dzau VJ. N Engl J Med. 1994;330: 1431-38

Atherosclerosis: A Progressive Process


Normal

Fatty
Streak

Fibrous
Plaque

Occlusive
Atherosclerotic
Plaque

Plaque
Rupture/
Fissure &
Thrombosis

Unstable
Angina

MI

Coronary
Death

Stroke

Effort Angina
Claudication

Clinically Silent

Increasing Age

Courtesy of P Ganz.

Critical Leg
Ischemia

Impact of

Endothelial Dysfunction

Arteriosclerosis

Atheromas
and
Thrombosis

ENDOTHELIAL
DYSFUNCTION

Vascular Spasm

Arterial
resistances

Endothelial Dysfunction and Cardiovascular Disease


Vasospasm
Coronary, Cerebral
Reocclusion

Heart Failure
Thrombosis
Coagulopathy
Diabetic
Diabetic
Angiopathy
Angiopathy

Hypertension

Endothelial
Dysfunction

Reperfusion
Injury
Peripheral Artery
Disease

Hyperlipidemia
Immune Reaction
Atherosclerosis
Adapted from Rubanyi GM: J Cardiovasc Pharmacol.1993;22(suppl 4) S1-S14

Inflammatory
Disease

Shock:
the manifestation of cardiovascular failure.
"Acute circulatory failure with inadequate or
inappropriately distributed tissue perfusion
resulting in generalized cellular hypoxia.

Acute circulatory failure


Pump
Fluid
Tubing

Inability to supply adequate oxygen to match tissue


demand

Types of shock:
Cardiogenic shock

Obstructive shock
Acute myocardial infarction
Outflow obstruction ->pulmonary embolus
Acute aortic incompetence
Inflow obstruction -> Cardiac tamponade
Ischaemic mitral regurgitation
LV aneurysm
Myocardial contusion
~ 40% of myocardium damaged leading to
Shock

Hypovolaemic shock
Exogenous loss from haemorrhage
Endogenous loss -> third space loss & capillary leak syndrome

Distributive shock
A state of relative hypovolaemia (eg. loss blood oncotic pressure).
Impaired distribution and oxygen utilisation.
Classic examples: septic shock, spinal shock, anaphylactic shock, AV
shunting.

Let it
beat!

National High Blood Pressure Education Program

The Sixth Report of the

JOINT NATIONAL COMMITTEE


On Prevention, Detection,
Evaluation, and Treatment of

CLASSIFICATION OF BLOOD PRESSURE


FOR ADULTS AGE 18 AND OLDER
W H O 1999
JNC VI 1997
High Blood
Pressure

N ATIONAL INSTITUTES OF HEALTH

Normal
Category

SBP
(mmHg)

Hypertension
DBP

Category

Normal < 130 & < 85


High
Normal 130-139 or 85-89
Isolated systolic hypertension
Subgroup borderline

DBP

(mmHg) ( mmHg)

( mmHg)

Optimal <120 & < 80

SBP

Stage 1/
Grade1

140-159 or 90-99

Stage 2/
Grade 2

160-179 or 100-109

Stage 3/
Grade 3

180

140 and
140-149 and

or
< 90
< 90

110