Cardiac Pathophysiology

Pericarditis
Often local manifestation of another
disease
May present as:
Acute pericarditis
Pericardial effusion
Constrictive pericarditis

Acute Pericarditis
Acute inflammation of the pericardium
Cause often unknown, but commonly
caused by infection, uremia, neoplasm,
myocardial infarction, surgery or trauma.
Membranes become inflamed and
roughened, and exudate may develop

Symptoms:
Sudden onset of severe chest pain that
becomes worse with respiratory movements
and with lying down.
Generally felt in the anterior chest, but pain
may radiate to the back.
May be confused initially with acute
myocardial infarction
Also report dysphagia, restlessness,
irritability, anxiety, weakness and malaise
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Signs
Often present with low grade fever and sinus
tachycardia
Friction rub (sandpaper sound) may be
heard at cardiac apex and left sternal border
and is diagnostic for pericarditis (but may be
intermittent)
ECG changes reflect inflammatory process
through PR segment depression and ST
segment elevation.
5

Treatment
Treat symptoms
Look for underlying cause
If pericardial effusion develops, aspirate
excess fluid
Acute pericarditis is usually self-limiting,
but can progress to chronic constrictive
pericarditis
7

Pericardial effusion
Accumulation of fluid in the pericardial cavity
May be transudate
May be exudate
May be blood

Not clinically significant other than to indicate

underlying disorder, unless:
Pressure becomes sufficient to cause cardiac
compression cardiac tamponade
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Outcome depends on how fast

fluid accumulates.

If development is slow, pericardium can

stretch

If develops quickly, even 50 -100 ml of

fluid can cause problems

When pressure in pericardium = diastolic

pressure, get filling of right atrium,
filling of ventricles, cardiac output
circulatory collapse.
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Clinical manifestations
Pulsus paradoxus B.P. higher during
expiration than inspiration by 10 mm Hg
Distant or muffled heart sounds
Dyspnea on exertion
Dull chest pain
Observable by x-ray or ultrasound

10

Treatment
Pericardiocentesis
Treat pain
Surgery if cause is aneurysm or trauma

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Constrictive (chronic)
pericarditis
Years ago, synonymous with T.B.
Today, usually idiopathic, or associated
with radiation exposures, rheumatoid
arthritis, uremia, or coronary bypass graft

12

Pathophysiology:
Fibrous scarring with occasional
calcification of pericardium
Causes parietal and visceral layers to
adhere
Pericardium becomes rigid, compressing
C.O.
the heart
Stenosis of veins entering atria
Always develops gradually

13

Symptoms and Signs

Exercise intolerance
Dsypnea on exertion
Fatigue
Anorexia

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Clinical manifestations

Weight loss
Edema and ascites
Distention of jugular vein (Kussmaul sign)
Enlargement of the liver and/or spleen
ECG shows inverted T wave and atrial
fibrillation
Can be seen on imaging
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Treatment
Drugs and diet
Digitalis
Diuretics
Sodium restriction
Surgery to remove restrictive pericardium

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Cardiomyopathies
Disorders of the heart muscle
Most cases idiopathic
Many due to ischemic heart disease and hypertension.
Three categories:
Dilated ( formerly, congestive)
Hypertrophic
Restrictive

Heart loses effectiveness as a pump

17

Dilated cardiomyopathy

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Hypertrophic Cardiomyopathy

C.O. is normal, inflow resistance, and

mitral valve incompetence, arrhythmais
and sudden death.

19

Restrictive cardiomyopathy

Reduced diastolic compliance of the ventricle.

C.O. is normal or formation of thrombi,
dilation of left atrium, and mitral valve
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incompetence.

Disorders of the Endocardium:

Valvular dysfunction
Endocardial disorders damage heart
valves
Changes can lead to :
Valvular Stenosis = too narrow
Valvular Regurgitation = too leaky
(or insufficiency or incompetence)

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22

 Valves that are most often affected are the

mitral and aortic valves, but in I.V. drug users
and in athletes that inject performance
enhancing drugs, > 50 % involve only the
tricuspid valve.
Heart Murmur sound caused by turbulent
blood flow through damaged valves.
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Both types of valve disorders:

Cause increased cardiac work, and increased
volumes and pressures in the chambers.
This leads to chamber dilation and
hypertrophy.
Chamber dilation and myocardial hypertrophy
are compensatory mechanisms to increase
the pumping capability of the heart.
Eventually, the heart fails from overwork
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Aortic Stenosis
Three common causes:
Rheumatic heart disease -Streptococcus
infection damage by bacteria and autoimmune response
Congenital malformation
Degeneration resulting from calcification

25

Aortic Stenosis
Blood flow obstructed from LV into aorta during systole
Causes increased work of LV
LV dilation & hypertrophy as compensation
prolonged contractions as compensation
Finally heart overwhelmed
increased pressures in LA, then lungs, then right
heart
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Clinical manifestations

Develops gradually
Decreased stroke volume
Reduced systolic blood pressure
Narrowed pulse pressure
Heart rate often slow and pulse faint
Crescendo-decrescendo heart murmur
Angina, dizziness, syncope, fatigue
Can lead to dysrhythmias, myocardial
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infarction, and left heart failure

Mitral Stenosis
Most common of all valve disorders
Usually the result of rheumatic fever or bacterial
endocarditis
During healing the orifice narrows, the valves become
fibrous and fused, and chordae tendineae become
shortened
Get decreased flow from LA to LV during filling
Results in hypertrophy of LA

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 By causing LA to become pump:

Get increased pulmonary vascular pressures;
pressures increase through LA into lung
pulmonary congestion
lung tissue changes to accommodate increased
pressures
increased pressure in pulmonary artery
increased pressure in right heart
right heart failure
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Clinical Manifestations
Atrial enlargement can be seen on x-ray
Rumbling decrescendo diastolic murmur,
and accentuated first heart sound
Dyspnea
Tachycardia and risk of atrial fibrillation
Other signs and symptoms are of pulmonary
congestion and right heart failure
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Aortic Regurgitation
Caused by acute or chronic lesion of
rheumatic fever, bacterial endocarditits,
syphilis, hypertension, connective tissue
disorder (e.g.Marfan syndrome) or
atherosclerosis

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 Reflux of blood from aorta to LV during

ventricular relaxation.
Causes LV to pump more blood w/ each
contraction
LV hypertrophy
LV takes on globular shape
increased pressures in LA, lung, right
heart

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Clinical manifestations
Widened pulse pressure
Prominent carotid pulsations and
throbbing peripheral pulses
Palpitations
Fatigue
Dyspnea
Angina
High-pitched or blowing heart sound
during diastole

33

Mitral Regurgitation
Causes: mitral valve prolapse, rheumatic
heart disease, infective endocarditis,
connective tissue disorders, and
cardiomyopathy
Permits backflow of blood from the LV
into the LA during ventricular systole
Loud pansystolic murmur that radiates
into the back and axilla
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 Causes blood to flow simultaneously to aorta and back

to LA.
Both LV & LA pump harder to move same blood twice
LV hypertrophy and dilation as compensation
Compensation works awhile, then see C.O.
heart failure
Also LA hypertrophy
increased pressures through lungs pressures in right
heart right heart failure

Can see edema, shock

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Clinical Manifestations
Weakness and fatigue
Dyspnea
Palpitations

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Mitral Valve Prolapse

Cusps of valve billow upward into the LA during
ventricular systole
Mitral regurgitation can occur
Most common valve disorder in U.S.
Studies suggest an autosomal dominant inheritance
pattern
Many cases completely asymptomatic
Regurgitant murmur or midsystolic click

37

Clinical manifestations
Palpitations
Tachycardia
Light-headedness, syncope, fatigue,
weakness
Chest tightness, hyperventilation
Anxiety, depression, panic attacks
Atypical chest pain
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 Once considered to be a psychiatric malady

May have an autonomic dysfunction in which large
quantities of catecholamines are produced.
May be a normal variant
Can see:
chorda rupture
ventricular failure
systemic emboli and sudden death

actually associated with minimal morbidity and mortality

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Management

Echocardiography for diagnosis

Related to degree of regurgitation
Antibiotics before invasive procedures

blockers to relieve syncope, severe
chest pain, or palpitations
Avoid hypovolemia
Surgical repair
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General Treatment for Valve

disorders
Antibiotics for Strep
Anti-inflammatories for autoimmune
disorder
Analgesics for pain
Restrict physical activity
Valve replacement surgery

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Heart failure
Definition When heart as a pump is
insufficient to meet the metabolic
requirements of tissues.
Acute heart failure
65% survival rate

Chronic heart failure

Most common cause is ischemic heart disease
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Explanation of the terms

Myocardial failure = abnormalities reside in the myocardium and
lead to inability of myocardium to fulfilling its function

Circulatory failure = any abnormality of the circulation

responsible for the inadequacy in body tissue perfusion, e.g.
decreased blood volume, changes of vascular tone, heart
functiones disorders
Congestive heart failure = clinical syndrome which is
developed due to accumulation of the blood in front of the
left or right parts of the heart

General pathomechanisms involved in heart

failure development
Cardiac mechanical dysfunction can develop as a
consequence in preload, contractility and afterload
disorders
Disorders of preload
preload length of sarcomere is more than
optimal strength of contraction
preload length of sarcomere is well below the
optimal
opti
mal strength of contraction

Important: failing ventricle requires higher end-diastolic

volume to achieve the same improvement of CO
that normal ventricle achieves with lower
ventricular volumes
Disorders of contractility
In the most forms of heart failure the contractility of
myocardium is decreased (ischemia, hypoxia, acidosis,
inflammation, toxins, metabolic disorders... )
Disorders of afterload due to:
fluid retention in the body
arterial resistance
valvular heart diseases ( stenosis )

Characteristic features of systolic dysfunction

(systolic failure)
 ventricular dilatation
 reducing ventricular contractility (either generalized or
localized)
 diminished ejection fraction (i.e., that fraction of enddiastolic blood volume ejected from the ventricle
during each systolic contraction les then 45%)
 in failing hearts, the LV end-diastolic volume (or
pressure) may increse as the stroke volume (or CO)
decreases

Characteristic features of diastolic dysfunctions

(diastolic failure)






ventricular cavity size is normal or small

myocardial contractility is normal or hyperdynamic
ejection fraction is normal (>50%) or supranormal
ventricle is usually hypertrophied
ventricle is filling slowly in early diastole (during the
period of passive filling)
 end-diastolic ventricular pressure is increased

Causes of heart pump failure

A. MECHANICAL ABNORMALITIES
1. Increased pressure load
 central (aortic stenosis, aortic coarctation...)
 peripheral (systemic hypertension)
2. Increased volume load
 valvular regurgitation
 hypervolemia
3. Obstruction to ventricular filling
 valvular stenosis
 pericardial restriction

B. MYOCARDIAL DAMAGE

1. Primary
a) cardiomyopathy
b) myocarditis
c) toxicity (e.g. alcohol)
d) metabolic abnormalities (e.g.
(e.g. hyperthyreoidism)
hyperthyreoidism)
2. Secondary
a) oxygen deprivation ((e.g.
e.g. coronary heart disease)
b) inflammation (e.g. increased metabolic demands)
c) chronic obstructive lung disease

C. ALTERED CARDIAC RHYTHM

1. ventricular flutter and fibrilation

2. extreme tachycardias
3. extreme bradycardias

Pathomechanisms involved in heart failure

A. Pathomechanisms involved in myocardial failure
1. Damage of cardiomyocytes contractility,
compliance

Consequences:
defect in ATP production and utilisation
changes in contractile proteins
uncoupling of excitation contraction process
number of cardiomyocytes
impairment of relaxation of cardiomyocytes with decrease
compliance of myocardium

impaired of sympatosympato-adrenal system (SAS) number of

1-adrenergic receptors on the surface of cardiomycytes

2. Changes of neurohumoral control of the heart

function
Physiology: SNS contractili
contractility
ty
HR
activ
activity
ity of physiologic pacemakers

Pathophysiology
Pathophysiology:: normal neurohumoral control is
changed and creation of
pathologic neurohumoral
mechanisms are present

Pathophysiology of diastolic heart failure

systolic heart failure = failure of ejecting function of

the heart
diastolic heart failure = failure of filling the
ventricles, resistance to filling of ventricles

Diastolic failure is a widely recognized

clinical entity
But, which of the cardiac cycle is real diastole ?

Definition of diastolic heart failure

It is pathophysiological process characterized by symptoms and signs of
CHF, which is caused by filling resistance of ventricles and
intraventricular diastolic pressure

Primary diastolic heart failure

- no signs and symptoms of systolic dysfunction is present

- ! up to 40% of patients suffering from heart failure!
Secondary diastolic heart failure
- diastolic dysfunction is the consequence of primary
systolic dysfunction

Main causes and pathomechanisms of

diastolic heart failure
1. structural disorders
passive
passive chamber stiffness
a) intramyocardial
e.g. myocardial fibrosis, amyloidosis,
amyloidosis, hypertrophy,
myocardial ischemia...
ischemia...
b) extramyocardial e.g. constrictive pericarditis
2. functional disorders relaxation of chambers e. g. myocardial
ischemia, advanced hypertrophy of ventricles,
failing myocardium, asynchrony in heart
functions

Causes and mechanism participating on

impaired ventricular relaxation
a) physiological changes in chamber relaxation due to:
prolonged ventricular contraction
Relaxation of ventricles is not impaired !

b) pathological changes in chamber relaxation

due to: Impaired relaxation process
delayed relaxation (retarded)
incomplete (slowed) relaxation

 Consequences of impaired ventricular relaxation

- filling of ventricles is more dependent on diastasis
and on the systole of atrias than in healthy subjects

Symptoms and signs:

exercise intolerance = early sign of diastolic failure
coronary blood flow during diastole

Causes and mechanisms involved in

development of ventricular stiffness
ventricular compliance = passive property of ventricle
Source of compliance: cardiomyocytes and other heart
tissue to stretching

 Ventricular compliance is caused by structural

abnormalities localized in myocardium and in
extramyocardial tissue

a) Intramyocardial causes : myocardial fibrosis,

hypertrophy of ventricular wall,restrictive
cardiomyopathy
b. Extramyocardial causes : constrictive pericarditis
The role of myocardial remodelling in genesis of
heart failure
adaptive remodelling of the heart
pathologic remodelling of the heart

Main causes and mechanisms involved in

pathological remodelation of the heart
1.Increased amount and size of myocytes = hypertrophy
Due to: - volume and/or pressure load
(excentric, concentric hypertrophy)
- hormonal stimulation of cardiomyocytes by
norepinephrine, angiotenzine II
2. Increased % of non-myocytic cells in myocardium
and their influence on structure and function of heart
a. endothelial cells endothelins : mitogenic ability
stimulation growth of smooth muscle cells of vessels,
fibroblasts
b. fibroblasts - production of kolagens

Symptoms and signs of heart failure

1. forward failure:
symptoms result from inability of the heart to pump
enough blood to the periphery (from left heart), or to
the lungs (from the right heart)
a) forward failure of left heart:- muscle weakness, fatigue,
dyspepsia, oliguria....
general mechanism: tissue hypoperfusion
b) forward failure of right heart: - hypoperfusion of the
lungs disorders of gas
exchange
- decreased blood supply
to the left heart

2. backward failure:
symptoms result from inability of the heart to accept
the blood comming from periphery and from lungs

a. backward failure of left heart:

increased pulmonary capillary pressure dyspnoea
and tachypnoea, pulmonary edema (cardiac asthma)
arterial hypoxemia and hypercapnia....
b. backward failure of right heart:
increased pressure in systemic venous system
peripheral edemas, hepatomegaly, ascites
nocturnal diuresis....

Ischemic Heart Disease

Coronary Artery Disease (CAD),
myocardial ischemia and myocardial
infarction are progression of conditions
that impair the pumping ability of the
heart by depriving it of oxygen and
nutrients.

62

Coronary Artery Disease

Any vascular disorder that narrows or
occludes the coronary arteries.
Most common cause is atherosclerosis

63

 The arteries that supply the heart are the first branches
off the aorta
Coronary artery disease decreases the blood flow to
the cardiac muscle.
Persistent ischemia or complete occlusion leads to
hypoxia.
Hypoxia can cause tissue death or infarction, which is a
heart attack, which accounts for about one third of all
deaths in U.S.
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Risk Factors

Hyperlipidemia
Hypertension
Diabetes mellitus
Genetic predisposition
Cigarette smoking
Obesity
Sedentary life-style
Heavy alcohol consumption
Higher risk for males than premenopausal women

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Myocardial Ischemia
Myocardial cell metabolic demands not met
Time frame of coronary blockage:
10 seconds following coronary block
Decreased strength of contractions
Abnormal hemodynamics

See a shift in metabolism, so within minutes:

Anaerobic metabolism takes over

Get build-up of lactic acid, which is toxic within the cell
Electrolyte imbalances
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Loss of contractibility

 20 minutes after blockage

Myocytes are still viable, so
If blood flow is restored, and increased aerobic
metabolism, and cell repair,
Increased contractility

About 30-45 minutes after blockage, if no relief

Cardiac infarct & cell death
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Clinical Manifestations
May hear extra, rapid heart sounds
ECG changes:
T wave inversion
ST segment depression

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Chest Pain
First symptom of those suffering myocardial ischemia.
Called angina pectoris (angina pain)
Feeling of heaviness, pressure
Moderate to severe
In substernal area
Often mistaken for indigestion
May radiate to neck, jaw, left arm/ shoulder

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 Due to :
Accumulation of lactic acid in myocytes or
Stretching of myocytes

Three types of angina pectoris:

Stable, unstable and Prinzmetal

70

Stable angina pectoris

Caused by chronic coronary obstruction
Recurrent predictable chest pain
Gradual narrowing and hardening of vessels
so that they cannot dilate in response to
increased demand of physical exertion or
emotional stress
Lasts approx. 3-5 minutes
Relieved by rest and nitrates

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Prinzmetal angia pectoris

(Variant angina)
Caused by abnormal vasospasm of normal vessels
(15%) or near atherosclerotic narrowing (85%)
Occurs unpredictably and almost exclusively at rest.
Often occurs at night during REM sleep
May result from hyperactivity of sympathetic nervous
system, increased calcium flux in muscle or impaired
production of prostaglandin
72

Unstable Angina pectoris

Lasts more than 20 minutes at rest, or
rapid worsening of a pre-existing angina
May indicate a progression to M.I.

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Silent Ischemia
Totally asymptomatic
May be due abnormality in innervation
Or due to lower level of inflammatory
cytokines

74

Treatment
Pharmacologically manipulate blood pressure, heart
rate, and contractility to decrease oxygen demands

Nitrates dilate peripheral blood vessels and

Decrease oxygen demand
Increase oxygen supply
Relieve coronary spasm
75


blockers:
Block sympathetic input, so
Decrease heart rate, so
Decrease oxygen demand
Digitalis
Increases the force of contraction
Calcium channel blockers
Antiplatelet agents (aspirin, etc.)

76

Surgical treatment
Angioplasty mechanical opening of
vessels
Revascularization bypass
Replace or shut around occluded
vessels

77

Myocardial infarction
Necrosis of cardiac myocytes
Irreversible
Commonly affects left ventricle
Follows after more than 20 minutes of
ischemia

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Structural, functional
changes
Decreased contractility
Decreased LV compliance
Decreased stroke volume
Dysrhythmias
Inflammatory response is severe
Scarring results
Strong, but stiff; cant contract like healthy cells

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Clinical manifestations
Sudden, severe chest pain
Similar to pain with ischemia, but stronger
Not relieved by nitrates
Radiates to neck, jaw, shoulder, left arm

Indigestion, nausea, vomiting

Fatigue, weakness, anxiety, restlessness and
feelings of impending doom.
Abnormal heart sounds possible (S3,S4)
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 Blood test show several markers:

Leukocytosis
Increased blood sugar
Increased plasma enzymes
Creatine kinase
Lactic dehydrogenase
Aspartate aminotransferase (AST or SGOT)

Cardiac-specific troponin

81

ECG changes
Pronounced, persisting Q waves
ST elevation
T wave inversion

82

Treatment
First 24 hours crucial
Hospitalization, bed rest
ECG monitoring for arrhythmias
Pain relief (morphine, nitroglycerin)
Thrombolytics to break down clots
Administer oxygen
Revascularization interventions: by-pass grafts, stents
83
or balloon angioplasty