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Consequences of ischemia:

metabolic changes: ATP depletion, lokal acidosis, increased inflow of
calcium to the cells

impaired contractility (decrease of stroke volume):

impaired relaxation (diastolic dysfunction)

impaired electrical events (arrhytmias, ECG)

morphological changes (myocytes, necrosis, fibrotisation, steatosis
etc.)

clinical symptoms (pain, arrhytmia, heart failure)
Postischemic changes
* ischemia duration
* reperfusion
Stunned myocardium
perfused but not functioning
reversible continuous dysfunction of myocardium after
reperfusion without apparent changes
Hibernating myocardium
chronically hypoperfused and functionally impaired
situation with continuously decreased blood flow accompanied by impaired contractility
adaptation of cells to decreased energy delivery
Ischemic preconditioning
increased resistence of myocardium against damage due to ischemia
caused by preceding ischemia and reperfusion
Secondary hypertension
• Is due to some other cause
(endocrine, kidney disease,
medication
• Up to 12% of hypertensive
patients
• Endocrine:
– Primary hyperaldosteronism
(Conn’s syndrome)
– Secondary hyperaldosteronism
– Cushing syndrome
– Pheochromocytoma
– Acromegaly
– Estrogen therapy
– Pregnancy
• Renal disease
– Stenosis of renal artery (unilateral
= increased activity RAAS; bilateral
= RAAS and decreased filtration)
– Renal parenchymal disease
• Other
– Coarctation of aorta
Cardiac output and blood pressure
depend on:
• Characteristics of the heart:
• Contractility
• Frequency
• Characteristics (diameter) of the vessels
• Tone of arteriols influences mainly resistence
• Tone of veins (or less mid-size arteries) influences the
volume of vascular bed. Volume of the bed is connected to
pressure and vascular tone (compliance)
• Volume of circulating blood
Kidney-fluid mechanism of pressure
control
Heart and vessels are regulated
by mechanisms that are of a
proportional controller type.
Kidney fluid regulator is a
integral (I) controller type. (its
long term sensitivity/gain is
infinity)
= kidneys excrete more fluid
until the pressure is set exactly
on the equilibrium (reference)
value
Increased
peripheral
resistance is
common
in hypertensive
individuals, but
it is not the
main cause
1. hyperkinetic
2. postcapillary
3. precapillary
restrictive – loss of pulmonary tissue
obstructive – thromboembolism
active-vasoconstrictive – hypoxia
4. pulmonary arterial hypertension
Hypoxic pulmonary hypertension
-many lung diseases, mainly chronic
obstructive disease, alveolar hypoventilation,
severe obesity, lung fibrosis
-high altitude
-syndrome of sleep apnoe
mainly obstructive (relaxation of muscles…)
apnoe over 10 sec, often even several dozens
dozens or hundreds of such episodes during the night
decreased ventilation and oxygen saturation
Shock
=
Sudden, life threatening disorder of overall tissue
perfusion and circulatory system failure
Adequate perfusion is necessary for proper functioning of
tissues and indeed, survival of whole organism
Tissue perfusion depends on perfusion pressure
Hypovolemic shock
Clinical picture is determined partly by hypovolemia
(decrease of systolic pressure, oliguria / anuria...), partly by
compensation mechanisms (tachycardia, increased
periferal resistence, redistribution of blood...)
• Increased peripheral vessel resistence (cold sweaty acral
parts, so called cold hypotension from hypovolemia) x
peripheral=distribution shock
• Decreased central venous pressure
• Mortality about 20%
Cardiogenic shock
= Critical decrease of cardiac output, due to
decrease of contractility of heart as a whole
(i.e. failure of cardiac pump)
Mechanisms:
 Necrosis / large part of heart muscle is lost (most frequently
extensive anterior MI), supposed loss of >40% myocardium
or less in already altered myocardium (repeated MI, chronic
heart failure, cardiotoxic substances / medicaments,
metabolic faktors)
 malignant tachy / brady-arrhythmia (ventricular fibrilation x
extreme bradycardia), MV = SV x f
 Wall, papillary muscle or chordae tendineae rupture
Obstructive shock
Most common features akutní obstrukce:
- Heart tamponade
- Large pulmonary embolism
- other (acute) block/compression of pulmonary circulation or
inferior vena cava
Peripheral = distributive shock
= Alteration of circulation caused by a decreased peripheral
resistance, lost venous tone and and/or movement of fluid to
extracellular space
1. Anaphylactic shock
2. septic/ toxic shock
3. Neurogennic shock
4. Some endocrine based shocks
Peripheral = distributive shock
1. Anaphylactic shock
• Starting mechanism: Reaction of antigens
with IgG (as opposed to atopy, where IgA is
involved)
• mediators of histiocytes, mast cells etc are
released (histamine, serotonin, SRS-A...),
• generalized vasodilation and an increased
peripheral permeability
(very fast development - seconds to minutes)
Peripheral = distributive shock
2. septic/toxic shock
Occurs in 25% Gram- bacteremias (Escher. coli, pseudomon...)
and
5% Gram+ bacteremias (Staphyloc., Streptoc. betahemolyticus, pneumococci)
Pathogenesis:
Exaggerated defence reaction (SIRS):
bacterial antigen (LPS)  macrophage activation  TNF, IL1  endotel  NO  vasodilation
Develops during hours or days, 50 % mortality
6 Systemic inflammatory response
syndrome (SIRS)
Definition
• Delocalized and dysregulated inflammation process of high
intensity. It leads to disorders of microcirculation, organ
perfusion and finally to secondary organ dysfunction.
• This secondary dysfunction is not due to primary insult, but
due to autoaggressive systemic inflammatory response of the
organism to the primary insult.
• This systemic inflammatory response syndrome (SIRS), leads
without therapeutic intervention to multiple organ
dysfunction syndrome (MODS) and death.
8 Pathophysiology of SIRS
Insult
• hypoxic-reperfusion damage
• infection (endotoxin, other microbial toxins or microorganisms)
• primary mediators -histamin, anaphylatoxins C3a, C5a
• complexes antigen-antibody
• thrombin a plasmin (DIC)
Defensive reactions
• First detected signs of defense after insult are local and generalized
hemodynamic changes (vasodilatation, vasoconstriction).
Regulation of hemodynamic changes
• systemic sympathic-adrenal activation (changes in organ blood
distribution of minute volume)
• local microcirculatory changes - mediators produced by endothelial
cells and other inflammatory systems
(NO, PGI2 x
endothelin-1, thromboxan A2)
Endothelial cells reaction
Endothelial stimulation
• Key process in development of microcirculatory disorders
• release of protective mediators (vasodilatatory and antithrombotic)
• contraction of endothelial cells and P-selectin expression (adhesion of
neutrophils)
• aged endothelial cells desquamation, intracellular gaps, disturbances of
endothelial surface
• release of vasoconstrictive and prothrombotic mediators
• Result of stimulation process - thrombogenic vascular intima with increased
permeability.
Reversibility
• Fast stimulation of endothelium by primary mediators and development of
acute inflammatory response is process not dependent on proteosynthesis.
Endothelial cells are rapidly active, however, this activation without further
stimulation disappears within few minutes.
If insult persists (hours):
Activation of other inflammation components
•
•
•
•
•
•
•
•
•
activation of mononuclear cells - release of TNF- and
IL-1
adhesive receptors on mononuclear cells and tissue
factor release
endothelium activation: endothelial cells activated by
cytokines - release of adhesive receptors, tissue factor
expression
endothelial cytoskeleton rebuilt to irreversible active
state
chemotaxis of neutrophils - activation (reactions
worsening hypoxia)
interstitial edema and microthrombotization
edema compresses lymphatic and blood stream
anaerobic metabolism of tissue cells (decrease of pH optimal for hydrolytic enzymes)
hypoxia and organ dysfunction
Reversibility
•
Activation of mononuclear cells and release of
TNF- a IL-1 is inhibited by corticosteroids
released after activation of hypothalamicadrenal stress reaction. Those acute
microcirculatory disorders can be reversible, if
the insult is eliminated and appropriate
intensive care started.
Tissue damage
The degree of reversibility of secondary MODS
is influenced by:
• necrotic tissue damage
• changes of vessel wall caused by
proinflammatory cytokines
• during chronic process - proliferation of less
valuable cells (fibroblasts)
• apoptosis (induced during SIRS)
9 Diagnosis of SIRS
Diagnostic criteria - a weak part of SIRS theory.
• Official diagnostic criteria SIRS (Tab.) are not able
to cover dynamics and degree of SIRS.
Symptoms
Assessed factors
Body temperature
>38oC or <36oC
Pulse rate
>90 /min
Rate of breathing or
PCO2 (arterial blood)
Frequency of breathing >20 /min
PaCO2 <32 mm Hg
White blood count or
I/T ratio
>12 000/mm3 or <4 000/m3
>10%
SIRS diagnosis
Presence of SIRS indicated by presence of minimum 2 of
described signs. (Bone et al., 1992).
Aortic stenosis
(ejection click)
Pulmonary stenosis
Mitral insufficiency/
septal defect
Aortic insufficiency
Mitral stenosis
(opening snap)
Mitral stenosis
Patent ductus
arteriosus
Aortic stenosis
Mitral stenosis
Aortic insufficiency
Mitral insufficiency
Congenital
Rheumatic
Cusp abnormalities
Endocarditis
Rheumatic
Calcific
Rheumatic,
endocarditis
Infarction
Degenerative
Congenital
Dilation
Trauma
Collagen-vascular
disease
Aneurysm,
connective tissue
disorder
Degeneration
Inflammation
Rheumatic
Arthritic diseases,
syphylis
Angina pectoris
Dyspnea,
hemoptysis,
ortopnea
Dyspnea,
hemoptysis,
ortopnea
Syncope
Palpitations
Dyspnea
Palpitations
Congestive failure
Neurological
Hyperdynamic
pulses
Fatigue
Shunt malformation
Cyanosis depends on:
-Underlying anatomical defect and
- pressure conditions (blood flows from the area
Of higher pressure to area of lower pressure).
Pressure conditions can change if
the marformation persists for a long time
(shunt reversal)
1) Ventricular
septal defect
2) Subpulmonary
stenosis
(obstruction)
3) Aorta on the
VSD
4) Right ventricle
hypertrophy
Angina pectoris (AP)

stable: fixed stenosis
atherosclerotic plaque decreases coronary
reserve, increased oxygen requirements of
myocardium (tachycardia) ... subendocardial
ischemia
Other contributing factors: anemia,
increased blood viscosity, diastolic
hypotension, hypertrophy of myocardium
 vasospastic (Prinzmetal’s):
spasmus of epicardial artery,
transmural ischemic changes;
in rest (frequently nocturnally),
reperfusion may be accompanied by arrythmia
Acute coronary syndromes
unstable AP + acute MI
Unstable AP: unstable stenosis
rupture, thrombosis, spasmus,
uncomplete obturation + shorter time of
ischemia
without necrosis
Preload
filling of the heart at the end of the diastole
enddiastolic volume = EDV
Frank-Starling mechanisms
Volume in the ventricle corresponds to the pressure –
enddiastolic pressure, EDP, filling pressure
Factors influencing preload
- Venous return
total blood volume
blood distribution (position of the body, intrathoracic
pressure, venous tonus…)
- atrial systole
- size of ventricle cavity
- intrapericardial pressure
Low preload is the cause of the decreased CO in case of
syncope and shock
In heart failure the preload is not decreased but it is
increased as one of the the compensatory mechanisms
J.Kofránek
intraventricular pressure
EDP
ventricle volume
Endothelium
Main functions:
* regulated permeability
* regulation of vasodilatation and vasoconstriction
* vessel integrity
Functional endothelium:
VD: nitric oxide – NO, prostacyclin (PGI2)
VC: endothelin, angiotensin II
impedes platelets and leukocytes adhesion and aggregation
anticoagulant – trombomoduline
regulation of fibrinolysis: tPA + PAI-1
Endothelial function reflects a balance
between factors such as nitric oxide (NO), which promotes
vasodilatation and inhibits inflammation and vascular
smooth muscle proliferation,
and endothelial-derived contracting factors, which increase
shear stress and promote the development of atherosclerosis.
Current evidence suggests
that endothelial status is not determined solely by individual
risk factor such as lipids, hypertension, and smoking,
but by an integrated index of all
the atherogenic and atheroprotective factors
present in an individual, including known
and as yet unknown variables and genetic predisposition.
Endothelial dysfunction:
imbalance between vasoactive and
procoagulant/fibrinolytic factors
* vasoconstriction
* inhibition of fibrinolysis
* leucocyte adhesion (selectins…)
* increased permeability
* procoagulant activity
* release of cytokins
Pathogenesis of atherosclerosis
Damage to the endothelium – shear stress, smoking, infection ?,
hypertension...
Macromolecules and cell penetration – LDL, monocytes
Macromolecules and cell retention – LDL, monocytes-macrophages
LDL modification: oxidation, glycation, aggregation
LDL accumulation in the macrophages – foam cells
Inflammation – production of reactive oxygen species, cytokines, growth
factors, enzymes...
N.Engl.J.Med., 2000
Fibrous changes – fibrous cap
N.Engl.J.Med., 2000
Advanced lesion and thrombosis
plaque stability –
necrotic debris,
inflammatory activitity
neovascularisation + hemorrhage
thinning of the fibrous cap
calcifications
ulcerations
injury to the plaque, intraplaque bleeding...
Nature, 2000
Sequelae of the necrosis
• hemodynamic (disturbances of contractility, decrease
of ejection fraction) – large necrosis or repeated
infarction - heart failure, if about 40% of myocardium
destroyed, cardiogenic shock can develop
• electrical instability – arrhytmias, ventricular
fibrillation, sudden death
• remodelation of the ventricle – scarring, aneurysma
(dyskinesis, thrombosis with embolism), dilatation –
importance for prognosis
• rupture of the wall, aneurysma (pericardial
tamponade), septum, papillary muscle
Intraventricular
pressure
insufficiency
..smaller stroke volume
Stroke
volume
Stroke
volume
Stroke
volume
increased stroke volume
Increase in preload
Ventricular volume
Minute
cardiac
output
insufficiency
increased stroke volume
Lowering of “Starling curve”
smaller stroke volume
greater preload
End-diastolic pressure
Cardiomyopathy
Definition:
= chronic disorder of myocardium with abnormal
ventricular both function and morphology
weakening of the heart muscle or a change in heart
muscle structure
prolonged course, slow progression
Pathogenesis:
“universal” reaction of cardiac muscle
on various noxa
→ inflammation, hypertrophy, degeneration,
necrosis, fibrosis
→ accumulation of lipids, glycogen, amyloid
Lipoid deposits in myocardium
Cardiomyopathy
Dilated CM
Restrictive CM
•
•
•
•
destruction of muscle fibers
dilatation without hypertrophy
Hypertrophic CM
•
•
asymmetric hypertrophy
obstruction of LV offtake
subendocard. fibrosis
arrhythmia
Cardiomyopathy
Secondary:
infectious
bacterial
viral (coxsackie)
ricketsia
mycosis
parasitic (Chagas dis.)
toxic (alcohol, Co, narcotics, psychofarmacs, adriamycin, prokainamid)
endocrine / metabolic (↓T4, ↑T4, ↑GH, uremia, ↓vit.B1, K, Mg)
allergy, autoimmunity (immunocomplex., SLE, sarkoidosis…)
Restrictive CM
Characteristics:
♥ subendocardial fibrosis (event. eosinophil infiltration)
♥ frequent arrhythmia
♥ heart is normal in size or only slightly enlarged
♥ rare form
amyloid deposits
Constrictive pericarditis and cardiac
tamponade
• Cardiac tamponade
manifests when
pressure in pericardial
cavity reaches values of
diastolic pressure in RV
and left atrial pressure
Atrial fibrillation
atrial activity: irregular f waves
AV conduction is absolutely irregular
The most common arrythmia
Ventricular fibrilation (or flutter)
Acute situation, hemodynamic arrest –
0 cardiac output, 0 pulsation, coma,
resuscitation
REENTRY
main cause of tachyarrhytmias
- two pathways proximally and distally connected
- different conductivity (slow)
- unidirectional conduction block of 1 pathway
ischemia, fibrosis
typically accessory pathways
Atrial (supraventricular) extrasystole (SVES)
spreading of impulse in the
ventricles is normal,
QRS complex is of normal shape/duration
Ventricular extrasystole
spreading of impulse in the
ventricles is abnormal,
QRS complex is different and longer
Compensatory pauses
in VES SA node cannot be
discharged
in SVES the impulse in SA node
is discharged by retrograde
conduction
AV block 2rd degree
AV block 3rd degree
Preexcitation,
WPW syndrome
Bundle branch blocks (raménkové blokády)
LBBB (left, levý)
RBBB (right, pravý)