Download Methodological Instruction to Practical Lesson № 7

MINISTRY OF PUBLIC HEALTH OF UKRAINE
BUKOVINIAN STATE MEDICAL UNIVERSITY
Approval on methodological meeting
of the department of pathophisiology
Protocol №
Chief of department of the pathophysiology,
professor
Yu.Ye.Rohovyy
“___” ___________ 2008 year.
Methodological Instruction
to Practical Lesson
Мodule 2 : PATHOPHYSIOLOGY OF THE ORGANS AND SYSTEMS.
Contenting module 5. Pathophysiology of blood circulation
and respiratory system.
Theme 7: PATHOPHYSIOLOGY OF THE HEART, CARDIVASCULAR SYSTEM.
Chernivtsi – 2008
1.Actuality of the theme. Strife with a heart insufficiency - major
problem of national public health services. Its national significance is determined
by a high morbidity and death rate, large labor losses, considerable traumatism.
The heart insufficiency often arises on ground of necrotic damages of cardiac
muscle. Quantity both coronarygenic and epinephrine and norepinephrine genesis
damages of the myocardium recently increases, which one result from a stress,
mental overstress, excessive phisical loads. The warning of necrotic, inflammatory,
metabolic, neuroendocrine and other damages of the myocardium is the constituent
of preventive maintenance of heart insufficiency. The new scientific direction preventive cardiology was now formed, problems by which one include warning
and early detection of cardiovascular system function disorders.
2.Length of the employment – 2 hours.
3.Aim:
To khow: etiology and risk factors of heart disease.
To be able: to analyse the heart hypertrophy.
To perform practical work: To analyse the compensatory mechanisms
cardio-vascular diseases.
4. Basic level.
The name of the previous
disciplines
1.
histology
2.
biochemistry
3.
physiology
The receiving of the skills
Histochemical structure of the myocardium.
Specialities of blood supply of heart.
The main physiological features of heart function.
Principle of operation of the electrocardiograph.
Technique of record of an electrocardiogram in three
standard leads.
Principal components of an electrocardiogram.
5. The advices for students.
1. There are three pathophysiologic heart insufficiency variants: 1.Heart
insufficiency because of overload. The main causes are high resistance to cardiac
out put, for example generall or pulmonary hypertension, heart apertures stenosis;
and big diastolic blood inflow, for example atriovenous fistulas, heart values
insufficiency, heavy physical work. 2.Heart insufficiency because of myocardium
damage. All causes are divided into four groups, as following: a) infectional and
toxic damages (different etiology myocarditis, alcohol myocardiopathy); b) total or
local hypoxia (coronary heart disease, pneumonia, obstructive bronchitis,
bronchial asthma; c) different metabolism disorders (metabolism of vitamins,
carbohydrate, protein, urine acid and others), in such cases insufficiency develops
even at normal or diminished heart load; d) neurotrophical and hormone abnormal
influences on the heart (continuous emotion al or physical stress, hyperthyreosis,
hyperfunction of suprarenal glands). 3.Mixed heart insufficiency variant. It arises
at combination of myocardium damage and its overload, for example at
rheumatism, when of inflammatory myocardium damage and valvular heart
violations are combined.
2. Stages of heart failure development. Heart failure has three stages of
development: first – emergency condition, second- stable adaptation (bouth these
stages display the compensation), and third – exhaustion (decompensation). If the
organism or some organs need more nutritious substances and O 2 the heart work is
increased in norm. At myocardium damage when the normally working
cardiomyocites amount is decreased and, as the result, is increased of each
cardiomyocites load or in heart overflow condition heart work is provided by the
alarm cardiac and extracardiac mechanisms (first stage).
3. Compensation mechanisms. Cardiac alarm mechanism are represented by the
increase of heart beats (in two time), systolic blood ejection (to 50%), heart blood
output per minute (in 4-5 time), each cardiomyocytes function and their
phosphorilative potential. Extracardial (out the heart) mechanisms are the
following: the increase of O2 utilization by all tissues and as the result, arterialvenous oxygen difference of blood increases, peripheral vassal resistance is
decreased. Cardiac adaptive mechanisms is most important. The increase of heart
beats number (tachycardia) provides the heart blood output constansy. It can
happen in the result of raised blood pressure in right atria cavity influence on
rhythm driver (sino-atrial ganglia), and also after
nervous and humoral
extracardial influences. Sodium and potassium ions penetration frequency (Na+
into the cells, K+out the cells) per minute is increased thus depolarization and
repolarization occurs more often. Diffusion of action potentials into the
sarcoplasmal reticulum membranes induces the penetration of Ca ++ ions and
cardiomyocites contractions. There are two compensation mechanisms the
increase of the cardiomyocytes contraction force: heterometric and homeometric.
Heterometric compensation mechanism (Franc-Starling) is inserted in blood
volume overload. Heart cavities blood inflow increase during diastole, which
increases of muscle fibres tension and the force of heart shortening during systole.
Dilatation of heart cavities is characterized by the increase of cardiac output (it’s
so-called tonogenic dilatation).
Homeometric compensation mechanism works during the increase of resistance
to cardiac output. Length of muscle heart fibres augments not so sharply in this
case, but high pressure and effort, that happened by reason of contraction of
muscle at the end of diastole. Force of cardiac contractions augments not at once,
but gradually with each following heart contraction, while will not arrive at level,
necessary for safety of constancy of minute volume-heart. Heterometric
compensation mechanism is more energy economic than homeometric. First stage
doesn’t boundless because it provokes the increase of the O2 using, the decrease of
diastole renewal time, myocardium rest and the decrease of hemodynamic heart
characteristic: during diastole the ventricles can’t blood filling normally, a systole
becomes less of full value, because of this mobilization of heterometric
compensation mechanism is impossible. The first stage doesn’t boundless because
there are limitary mechanisms. The increase of heart beats number and heart
contraction force leads to the decrease of ATP and creatinephosphate concentration
in working cardiomyocites. The glycolysis activation conduces H + ions
accumulation (lactic acid origin), which connects with troponin in place of Ca++
ions and violates actin-myosin interaction (defective systole and aqute heart
insufficiency may develop).
4. Myocardium hypertrophy.
Valuing biological myocardium hypertrophy sense, turn mind to internal
discrepancy of given phenomenon. On one hand, this is a prettily perfect
adaptative mechanism, which provides for a long time execution of raised work by
heart in normal and pathological conditions, on another – structure peculiarities
and functions of hypertrophied heart are by precondition for development of
pathology. Dominance first or second in each concrete case determines
peculiarities of pathological process. According to metabolism, structures and
myocardium functions disorders in phase of compensative heart hyperfunction
there are three stages.
1. Emergency stage develops directly after heart overload, it characterizes by
combination of pathological changes in myocardium (disappearance of glycogen,
decrease of creatinphosphate, intracellular potassium concentration decrease and
sodium one increase, stimulation of glycolysis and lactate accumulation). This
stage is characterized by the fast heart mass increase (during weeks) due to protein
synthesis and increase of muscle fibres thickness.
2. Stage of completed hypertrophy and steady hyperfunction. In this stage
myocardium mass is increased on 100 – 120 % and couldn’t longer increases.
Metabolism and structures of myocardium is normal; oxygen consumption, energy
synthezise, macroergic substances contents does not differ from norm, blod flow is
normalized. A hypertrophic heart is adaptated to new loading conditions.
3. Stage of gradual exhaustion of the heart and progressing of cardiosclerosis is
characterized by deep disorder of metabolism and structures in power-creating and
contractive elements of myocardium. Part of myocardiocytes dies and replaces by
connective tissue. Heart regularly apparatus is disturbed. Progressing of
compensatory mechanisms exhaustion leads to chronic heart insufficiency
development, and then to the blood circulation insufficiency.
5.Chronic heart insufficiency.
Chronic, or stagnant, heart insufficiency develops gradually, mainly by reason of
metabolic violations in myocardium at long time heart hyperfunction or at
different kinds of myocardium injury appearances. Because heart output is
decreased, blood supply of organs, which are localized on heart outflow ways,
diminishes. At the same time by reason of heart inability to pump all blood, that
comes to it, stagnation on blood inflow ways develops (in veins). As volume of
venous channel approximately in 10 time exceeds an arterial channel volume, a
considerable amount of blood nuddle together in veins. Blood insufficiency
acquires some specific signs in case of work violation mainly some heart ventricle
circulation and is called by insufficiency of left-ventricle type or right-ventricle
one. In first case blood stagnation is observed in veins of small blood circulation,
that can to be reason of lungs edema, in second case - in veins of big blood
circulation, in such case liver is enlarged, the edema of legs and ascites appears.
Violation of contractive myocardium function does not at once causes
development of the blood circulation insufficiency.
As adaptive mechanism at first peripheral arterioles resistance of big blood
circulation reflexly decreases, that relieves a blood flow to majority of organs.
Arterioles of small blood circulation reflexly narrow, thus to left atria blood inflow
diminishes and at the same time pressure in system of pulmonary capillaries
decreases. Last mechanism is the pulmonary capillaries protection from overflow
of the blood and it prevents of lungs edema development . There is typical some
function discord sequence of different heart departments. Consequently,
decompensation of strong left ventricle functions quickly causes violation of left
atria function, blood stagnation in small blood circulation and constriction of
pulmonary аrteriole But then a less stronger right ventricle is overloaden, that
leads to its decompensation and development of the right-ventricle type
insufficiency.
Hemodynamic indexes of chronic heart insufficiency change like so: heart volume
per minute decreases (from 5-5,5 to 3-4 l/min); speed of blood stream decreases in
2-4 times; arterial pressure changes a little; venous pressure rises; the capillaries
and postcapillares vein are dilated; a blood stream slows; pressure rises. The
pathological changes of other organs, which arise later, are the result of prescribed
changes.
Retardation of blood stream in big blood circulation system and violation of the
lung blood circulationin causes increase of renewed hemoglobin amount in blood.
Skin and mucous membranes have a typical blue colour (cyanosys). Tissues have
no adequate quantity of oxygen. Hypoxia is characterized by accumulation of
organic acids and CO2 that leads to acidosis development. Acidosis and hypoxia
results in violation of breathing regulation and causes dyspnoea. Erythropoiesis is
stimulated, general volume of circulatory blood and relative contents of blood cells
is increased too, all these changes display of hypoxia compensation, but in same
time are the reasen of blood viscosity increase and violation of blood hemodinamic
properties.
By reason of high pressure in capillaries and tissue acidosis an edema develops,
which, into its turn, reinforces hypoxia, because diffuse way from capillary to cell
is increased. The general violations of water and electrolytes metabolism (sodium
and water accumulation) streingthen stagnant edema. This is one more proof of
internal compensation mechanisms contradictions during pathological process.
Mechanisms, which evolutional happened for guaranteeing of salts and liquid
sufficient contentsfin organism in case of water loss and blood loss complicates of
patient condition in case of heart insufficiency. Surplus of common used in
patients blood, which have heart insufficiency, does not excret by kidneys like in
healthy man, and accumulates in organism together with equivalent water volume.
Violation of tissues nutrition at long time of the blood supply insufficiency causes
deep and inconvertible disorder of intracellular metabolism. It results in violation
of protein synthesis, especially ensime of respiratory metabolism ways, in
development of histotoxic type of hypoxia. These phenomena are typical for
terminal phase of circulatory insufficiency. Blood flow insufficiency in digestive
tract causes terrible exhaustion of the organism, so - called cardiac cachexia.
Pathophysiological mechanism of heart insufficiency another origin is a
cardiomyocites damage. It can be result of inflammation or dystrophy, genetic
defects, infection, intoxication or immunopathological processes, illnesses, which
cause myocardium hypoxia or metabolism violations (protein, lipid, mineral and
vitamin). Uneffective ATP synthezise or ATP using by cardiomyocytes can be
really. Processes of uneffective ATP synthezise arises in case of oxygen in come
insufficient to the cardiomyocyte, O 2 concentration decrease or ischemia, and
also at violation of oxidative substances in come, uneffective mitochondrias
functions, creatinekinase – creatinephosphate system system violation. Uneffective
ATP using arises in case of myofibril proteins and sarcoplasmal net damage and at
disorder of calcium ions, potassium, and sodium metabolism. Violation of
cardiomyocytes membrane structures by lipid peroxides, by free radicals and
hydroperoxyde can be one of damage mechanisms. Free radical oxidation can be
result of oxidative metabolism violation cardiomyocyte or antioxidant systems
insufficiency. First functions of specific membrane pumps (Na+, К+-АТP-ase,
Са++-АТP-ase) disturb, than gradually membrane penetrability and membrane
phospholipid damage arises. Violation of membrane results in change of sodium,
potassium, chlorine ions and water stream. It causes swelling of cell, and calcium
ions accumulation and development of calcium toxic effects. It is possible the
increase of α- and
β- adrenoreceptors amount and free catecholamine
concentration, that deepens a primary damage. In case of metabolism violations,
which turned in extremely long ways, death of cardiomyocytes is possible. The
number of working cardiomyocytes decreases and it leads to their overload, thus
mechanisms of compensations are the same as earlier prescribed.
6. Classification of coronary heart disease.
There are 4 main types clinical manifestations of coronary heart disease.
1. Stenocardia (angina pectoris)
a) Stenocardia of the stress;
b) Stenocardia of the rest
2. Myocardial infarction
3. Intermediate variants
a) Acute focal myocardial dystrophy;
b) Small focal myocardial infarction
4. Indolence CHD
a) Silent (asymptomatic) CHD;
b) Atherosclerotical cardiosclerosis
7. Etiology of coronary heart disease.
During CHD can be affected one or all of the major epicardial coronary arteries
and their branches and can be diffuse or localized to one area of a single vessel.
The main reason of the vessels injury is atherosclerosis that reduces blood flow.
Risk factors of the CHD are hypercholesterinemia, arterial hypertension, smoking
(especially for women), hypokinesia, obesity, old age, and mail sex.
Atherosclerosis causes narrowing of the coronary arteries. Metabolic demands of
the heart are increased with everyday activities such as mental stress, exercises,
and exposure to cold. In certain disease states, such as thyrotoxicosis, the
metabolic demands may be so excessive that blood supply is inadequate despite
normal coronary arteries. In other situations, such as aortic stenosis, the coronary
arteries may not be diseased, but the perfusion pressure may be insufficient to
provide adequate blood flow. Symptomatic myocardial ischemia (angina pectoris)
and silent, or painless, myocardial ischemia are important functional indicators of
active CHD and increased risk of myocardial infarction or sudden death. The term
angina pectoris is derived from a Latin word meaning to choke. Angina pectoris
(stenocardia) is a symptomatic paroxysmal chest pain or pressure sensation
associated with transient myocardial ischemia. The pain typically is described as
constricting, squeezing, or suffocating. It usually is steady, increasing in intensity
only at the onset and end of the attack. The pain of angina commonly is located in
the precordial or substernal area of the chest; it is similar to myocardial infarction
in that it may radiate to the left shoulder, jaw, arm, or other areas of the chest (in
some persons may be epigastric pain).
8. Stenocardia.
Classic angina, sometimes-called exertion angina is associated with atheroslerotic
disease that produces fixed obstruction of the coronary arteries. It occurs when the
metabolic needs of the myocardium exceed the ability of the occluded coronary
arteries to deliver adequate blood flow during physical exertion, emotional stress,
or exposure to cold. The adrenalin blood concentration in such conditions
increases, so rate and force of the heart contractions and O 2 need increase too.
Adequate dilation of the heart vessels is impossible in the condition when coronary
arteries are inelastic. Adrenalin excess violates cardiomyocytes metabolism and
electrolyte balance.
The syndrome of variant angina or Prinzmetal’s angina was first described
Prinzmetal. It is caused by spasm of the coronary arteries; this condition is also
called vasospastic angina. Unlike the classic form of angina, which occurs with
exertion or stress, variant angina usually occurs during rest, smoking or with
minimal exercises, and frequently occurs nocturnally. The mechanism of coronary
vasospasm is uncertain. It may be the result of hyperactive sympathetic nervous
system responses, the result of calcium metabolism defect in vascular smooth
muscle, or the result of reduced syntheziseof prostaglandin I 2 or NO, which
promotes vasodilation. Arrhythmias often occur when the pain is severe; ECG
changes include ST segment elevation or depression, T- wave peaking, rhythm
disturbances.
Unstable angina is the result of atherosclerotic plaque disruption. Because of its
propensity to lead to infarction, it is some times referred to as preinfarction angina.
Plaque disruption may occur with or without thrombosis, it increases the degree of
coronary artery obstruction. When the plaque injury is mild, intermittent
thrombotic occlusion may occur and cause episodes of anginal pain at rest.
Vasoconstricting factors (thromboxane, serotonin, and platelet-derived growth
factor) are released from platelets that aggregate at the site of injury. These platelet
factors contribute, even at rest, to episodes of reduced coronary blood flow and
silent or symptomatic myocardial ischemia. Thrombus formation can progress until
the coronary artery becomes occluded, leading to myocardial infarction.
Silent myocardial ischemia occurs in the absence of anginal pain. The factors that
cause silent myocardial ischemia appear the same – impaired blood flow in the
result of coronary atherosclerosis or vasospasm. The reason for the painless
episodes of ischemia is unclear. The episodes may be shorter and involve less
myocardial tissue than those producing pain. Another explanation is that persons
with silent angina have defects in pain threshold, pain transmission, or automatic
neuropathy with sensory denervation. There is evidence of an increased incidence
of silent myocardial ischemia in person with diabetes mellitus, probably the result
of autonomic neuropathy, which is a common complication of diabetes.
Myocardial infarction. Myocardial infarction is ichemical necrosis of the
myocardium that develops in the result of sharp decrease or stop blood flow
through some area of the heart. Now, it is the most prevalent disease in the world,
number patients, which suffer myocardial infarction increase.
9. Etiology of myocardial infarction
The main reason of myocardial infarction is atherosclerosis of the coronary
arteries. The main proves are the results of pathological anatomy dissection of the
body patients with myocardial infarction, which died. Atherosclerotical plaques on
the coronary artery wall were discovered in 90-95 % cases. Acute myocardial
infarction may be the result of rupture or fissuring of an atherosclerotical plaque
and thrombus formation that interrupts blood flow. Some time it is the result of
thrombembolism or prolonged severe vasospasm, as in Prinzmetal’s variant
angina.
10. Pathogenesis of myocardial infarction.
All mechanisms of myocardial infarction beginning can be divided in two groups:
first group mechanisms (start mechanisms) provoke acute myocardial ischemia in
the result of blood flow violation and second group includes mechanisms of
myocardium necrosis.
Mechanisms of acute myocardial ischemia. Growing up of atherosclerotical
plaque decreases coronary artery diameter, violates blood flow through same area
of the heart, especially in left ventricle, complicates myocardium nutrition and may
cause development so-called critical stenosis and necrosogenic ATP deficiency.
Atherosclerotical injury of vessel strengthens its sensitivity to vasospastic
influences. It results from violation of NO (vasodilation agent) synthesis by
endotoliocytes because NO-synthase activity in such vessel is very decreased.
Atherosclerotical vessel injury reduces anticoagulative blood properties because
heparin concentration is decreased. This substance is used for lipoproteinlipase
activation in hyperlipoproteinemia condition (it is the main risk factor of
atherosclerosis), besides injured vessel has reduced antithrombotic potential
(antithrombin III deficit), unmasked collagen fibers and fibronectin cause
thrombocytes activation, their adhesion, aggregation and then thrombin formation.
It is the resultant thrombus that interrupts blood flow. All these mechanisms lead to
development of acute myocardial ischemia and onset the mechanisms of
myocardiocytes necrosis.
Mechanisms of myocardium necrosis. Acute ischemia causes deficiency of the
energy substances supply (adenosinthreephosphate, creatinphosphate). It results
from the decrease of cytochromoxydase activity. Electrons transposition violates
and it very reduces Crebs cycle activity. Cardiomyocytes use
adenosinthreephosphate and creatinphosphate but restoring of their concentration
is inadequate. ADP, AMP, adenosine and inorganic phosphate are accumulated in
cardiomyocytes. Energy deficit leads to oppression of Na,K-ATPase and CaATPase activity. Insufficiency of Na,K-ATPase activity causes violation of
repolarization, Na+ accumulates in the myocardiocytes, myocardium becomes
electrically unstabilized and inhomogeneous. These changes contribute to cardiac
fatal arrhythmias and sudden death, usually as the result of ventricular fibrillation.
During the period of impaired blood flow, injured and ischemic cells revert to
anaerobic metabolism, with accumulation of organic acids (especially lactic), much
of which is released into the local extracelullar fluid. The necrotic cells become
electrically inactive, and their membranes become disrupted, such that their
intracellular contents, including potassium, are released into the surrounding
extracellular fluid. This causes local areas of hyperkalemia, which can affect the
membrane potentials of functioning myocardial cells. As a result of membrane
injury and local changes in extracellular potassium and pH levels, some parts of
the infracted myocardium are unable to conduct or generate impulses, other areas
are more difficult to excite, and still others are overly excitable. These different
levels of membrane excitability in the necrotic, injured, and ischemic zones of the
infracted area set the stage for development of dysrhythmias and conduction
defects after myocardial infarction. Each of these zones in the infracted area
conducts impulses differently. Typical ECG changes associated with death of
myocardial tissue include prolongation of Q wave, elevation of the ST segment,
and inversion of the T wave. Ca2+ accumulation results from Ca-ATPase activity
oppression, it contributes to cardiomyocytes contracture (cardiomyocytes can not
relax), and mitochondriaes damage (Ca2+ excess can be accumulated in
mitochondriaes) that make worse energy deficit. Because many enzymes are
blocked, Crebs cycle violation leads to accumulation of acetylcoensim A and fat
acids. Fat acids oxidation in the β-cycle is impossible because this cycle needs
ATP, so concentration of fat acids in cardiomyocytes increases. These substances
have ability to dissolve membrane lipids and contribute to damage membrane ion
channels. The principal biochemical consequence of acute myocardial infarction is
the onset of anaerobic metabolism with inadequate production of energy to sustain
normal myocardial function. As a result, a striking loss of contractile function
occurs within 60 seconds of acute myocardial infarction onset. It results from H+
ions accumulation (metabolic acidosis develops). Lactic and piruvate acids
accumulation causes depress of creatinkinase activity, this enzyme controls
phosphates delivery to myofibrils. Besides, H+ ions obstruct Ca2+-troponin
interaction, so actin-myosin interaction is impossible in this condition, all these
depress of myocardiocytes contractile function. Phosphates accumulation, which
results from macroergic substances breakup, causes insoluble calcium phosphate
salt forming and then calcium ions concentration decrease in myocardiocytes.
Some time “reperfusion syndrome” (term reperfusion refers to reestablishment of
blood flow in ischemic area) results from the primary decrease of calcium ions
concentration. This phenomenon is characterized by the repeat damage of
myocardiocytes in the result of rapid come in myocardiocytes Ca 2+ ions because
big gradient concentration of calcium between blood and heart tissue in zone of
ischemia. This paradox arises at stress, during surgical treatment of coronary artery
occlusion or thrombolytic therapy. Calcium and catecholanimes cause
phospholipases activation; ischemia stimulates lipid peroxidation and exhausts
antioxidation system of the membrane protection. All these impair membranes,
violates membrane ion channels. Lysosomal membrane damage leads to
development myocardiocytes autolysis (it is necrosis which results from action
own cell enzymes). Myocardial cells necrosis causes release of different
myocardiocytes components that appear in the blood and are the diagnostic
markers (myoglobin, creatine kinase, lactate dehydrogenase, troponin).
Early reperfusion (within 15 to 20 minutes) after onset of ischemia can prevent
necrosis. Reperfusion after a longer interval can salvage some of the myocardial
cells that would have died owing to longer periods of ischemia. It may also prevent
microvascular injury that occurs over a longer period. Although much of the viable
myocardium existing at the time of reflow ultimately recovers, critical
abnormalities in biochemical function may persist, causing impaired ventricular
function. The recovering area of the heart is often referred to as stunned
myocardium. Because myocardial function is lost before cell death occurs, a
stunned myocardium may not be capable of sustaining life, and persons with large
areas of dysfunctional myocardium may require life support until the stunned
regions regain their function.
A myocardial infarct may involve the endocardium, myocardium, epicardium, or a
combination of these. Acute myocardial infarction can be divided into two major
types: transmural and subendocardial infarcts. Transmural infarcts involve the full
thickness of the ventricular wall and most commonly occur when there is
obstruction of a single artery. Subendocardial infarcts involve the inner one third to
one half of the ventricular wall and occur more frequently in the presence of
severely narrowed but still patent arteries.
Although gross tissue changes are not apparent for hours after onset of an acute
myocardial infarction, the ischemic area ceases to function within a matter of
minutes, and irreversible damage to cell occurs in about 40 minutes. The principal
biochemical consequence of acute myocardial infarction is the onset of anaerobic
metabolism with inadequate production of energy to sustain normal myocardial
function. As the result, a striking loss of contractile function occurs within 60
seconds of acute myocardial infarction onset. Changes in cell structure (glycogen
depletion and mitochondrial swelling) develop within several minutes. These early
changes are reversible if blood flow is restored. Irreversible myocardial cell death
occurs after 20 to 40 minutes of severe ischemia. Microvascular injury occurs in
about 1 hour and follows irreversible cell injury. If blood flow can be restored
within this 20- to 40-minute timeframe, loss of cell viability does not occur or is
minimal. The progression of ischemic necrosis usually begins in the
subendocardial area of the heart and extends through the myocardium to involve
progressively more of the transmural thickness of the ischemic zone. The extent of
the infarct depends on the location, rapidity of development, severity of coronary
vessel occlusion and vasospasm, amount of heart tissue supplied by the vessel,
duration of the occlusion, metabolic needs of the affected tissue, extent of
collateral circulation, and other factors such as heart rate, blood pressure.
Myocardial cells that undergone necrosis are gradually replaced with scar tissue.
An acute inflammatory response develops in the area of necrosis about 2 to 3 days
after infarction. Macrophages begin removing the necrotic tissue, they stimulate
fibroblasts proliferate activity and their ability of collagen fibrous synthesis; the
damaged area is gradually replaced with an ingrowth of highly vascularised
granulation tissue, which gradually becomes less vascular and more fibrous.
The stages of recovery from acute myocardial infarction are closely related to the
size of the infarct and the changes that have taken place within the infracted area.
Fibrous scar tissue lacks the contractile, elastic, and conductive properties of
normal myocardial cells; the residual effects and the complications are determined
essentially by the extent and location of the injury. Among the complications of
acute myocardial infarction are sudden death, heart failure and cardiogenic shock,
pericarditis and Dressler’s syndrome, thrombemboli, rupture of the heart, and
ventricular aneurysms.
Sudden death from coronary heart disease is death that occurs within 1 hour of
symptom onset. It usually is attributed to fatal dysrhythmias, which may occur
without evidence of infarction. About 30 % to 50 % of persons with acute
myocardial infarction die of ventricular fibrillation within the first few hours after
symptoms begin. Depending on its severity, myocardial infarction has the
potential for compromising the pumping action of the heart. Heart failure and
cardiogenic shock are dreaded complications. Cardiogenic shock is characterized
by the failure to eject blood from the heart, hypotension, and inadequate cardiac
output. Increased systemic vascular resistance often contributes to the deterioration
of cardiac function by increasing afterload or the resistance to ventricular systole.
The filling pressure, or preload of the heart, is also increased as blood returning to
the heart is added to blood that was previously returned but not pumped forward,
resulting in an increase of end-systolic ventricular volume. Increased resistance to
ventricular systole (afterload) combined with the decreased myocardial
contractility causes the increased end-systolic ventricular volume and increased
preload, which further complicate cardiac status.
Pericarditis may complicate the course of acute myocardial infarction. It usually
appears on the second or third day after infarction. The person experiences a new
type of pain that is sharp and stabbing and is aggravated with deep inspiration and
positional changes. Dressler’s syndrome describes the sings and symptoms
associated with pericarditis, pleurisy, and pneumonitis: fever, chest pain, dyspnea,
and abnormal laboratory test results (elevated leucocytes count and sedimentation
rate). The symptoms are the result of hypersensitivity response to tissue necrosis
(hyperergic inflammation), so anti-inflammatory agents or corticosteroid drugs
may be used to reduce the inflammatory response.
The acute postmyocardial infarction period can be complicated by rupture of the
myocardium, the interventricular septum, or a papillary muscle. Myocardial
rupture, occurring on the fourth to seventh day when the injured ventricular tissue
is soft and weak, often is fatal. Necrosis of the septal wall or papillary muscle may
also lead to the rupture of either of the structures, which worsening of ventricular
performance.
An aneurysm is an outpouching of the ventricular wall. Scar tissue does not have
the characteristics of normal myocardial tissue; when a large section of ventricular
muscle is replaced by scar tissue, an aneurysm may develop. This section of the
myocardium does not contract with the rest of the ventricle during systole. Instead,
it diminishes the pumping efficiency of the heart and increases the work of the left
ventricle, predisposing the patient to heart failure. Ischemia in the surrounding area
predisposes the patient to development of dysrhythmias, and stasis of blood within
the aneurysm can lead to thrombus formation.
5.1. Content of the theme. Three pathophysiologic heart insufficiency
variants. Stages of heart failure development. Compensation mechanisms.
Myocardium hypertrophy. Chronic heart insufficiency. Classification of coronary
heart disease. Etiology of coronary heart disease. Stenocardia. Etiology of
myocardial infarction. Pathogenesis of myocardial infarction.
5.2. Control questions of the theme:
1. Three pathophysiologic heart insufficiency variants.
2. Stages of heart failure development.
3. Compensation mechanisms.
4. Myocardium hypertrophy.
5.Chronic heart insufficiency.
6. Classification of coronary heart disease.
7. Etiology of coronary heart disease.
8. Stenocardia.
9. Etiology of myocardial infarction.
10. Pathogenesis of myocardial infarction.
5.3. Practice Examination.
Task 1. After the transferred flu in the patient with ischemic disease of heart the
signs of decompensation of cardiac activity have appeared. One of the
signs of it were edemas on the lower exstremity. Call leading link in their
pathogenesis.
A. Decrease albumins of blood B. Hyperproduction of vasopressine C.
Increase of permeability of vessels D. Increase of venous pressure E.
Delay of sodium by kidney
Task 2. In the patient with myocardial infarction the signs of hypoxia - dyspnea,
tachycardia,cyanosis of visible mucose membrans have appeared. The
development of hypoxia for him is connected with
A. Decrease quantity of erythrocytes B. Decrease hemoglobin content C.
Decrease of speed of bloodflow D. Lack oxygenation of blood E. Bad
dissociation of an oxyhemoglobin
Task 3. The patient died for myocardial infarction. The conducted histological
research of structure of the myocardium has found out considerable
contractive changes in the cardiomyocytes. It is conditioned by
accumulation in cardiomyocytes of ions
A. Potassium B. Sodium C. Calcium D. Magnesium E. Chlorine
Task 4. The patient with chronic heart insufficiency the cardiac output is reduced,
the venous pressure is increased, speed of bloodflow is sharply reduced,
there is an expressed acrocianosis, there are signs of stagnation in lungs.
The adequate mechanism of compensation in these conditions are
A. Increase of respiration rate B. Increse of an erythropoiesis
C. Throw out of erythrocytes from depot D. Increase of frequency of heart
rate E. Opening of additional of capillars
Task 5. The doctor - cardiologist has found out in the 40-year's woman with an
hypertension in examination on an electrocardiogram signs of hypertrophy
of ventricle. The general condition of the ill is satisfactory, complains does
not present. By the key-mechanism, which one provides compensation of
the heart insufficiency in this case, is the activation of proteins synthesis
A. Lysosomes B. Sarcoplasmic reticulum C. Cytoplasme
D. Membranes of cardiomyocytes E. Mitochondria
Real-life situations to be solved:
After transferred 3 months back anginas patient begin to be disturb by
dyspnea, gravity in the right hypochondrium, attacks of difficult breathing. The
edemas of the lower extremitus have appeared. At objective examination: dermal
covers with icteric colour, labiums cyanotic leg swollen. The cervical veins is
pulsing. The borders of heart are enlarged for expense of both ventricles, however
it is more left. Arterial pressure – 90/60 mm Hg. A respiration rate - 26/min. The
myocarditis, cardiovascular insufficiency in stage of compensation is detected.
1. What cause the damage of the myocardium in this patient?
2. What disorder testify about heart insufficiency?
3. Explain their pathogenesis?
4. What changes have compensatory – adaption significance?
5. What is their mechanism?
Literature:
1. Gozhenko A.I., Makulkin R.F., Gurcalova I.P. at al. General and clinical
pathophysiology/ Workbook for medical students and practitioners.-Odessa, 2001.
2. Gozhenko A.I., Gurcalova I.P. General and clinical pathophysiology/ Study
guide for medical students and practitioners.-Odessa, 2003.
3. Robbins Basic Pathology.-8th ed./Ramzi S.Cotnar, Vinay Kumar, Tucker
Collins.-Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.-2007.- 902 p.
4. Faller A., Schunke M., Schunke G. The Human body: An Introduction to
Structure and Function.-Stuttgard, New York: Thieme.-2004.- 710 p.