PATHOPHYSIOLOGY OF THE HEART

MINISTRY OF HEALTH OF UKRAINE

Bogomolets National Medical University

Department of Pathophysiology

​

Lecturer:

PhD Antsupova V.V.

CIRCULATORY SYSTEM

THE HEART AND ITS VALVES

​

Circulatory failure is a violation of hemodynamics, which is manifested in the fact that organs and tissues are not provided with the required amount of circulating blood, which, in turn, causes insufficient supply of oxygen, nutrients, disrupts the removal of end products of metabolism

​

EFFECTS

1. Violation of trophic supply of organs and tissues with reduced delivery of oxygen and nutrients.

​

• Disorders of removal from organs and tissues end products of metabolism.

​

​

INSUFFICIENCY �OF BLOOD CIRCULATION

​

• heart failure
• vascular insufficiency
• cardiovascular insufficiency

HEART LOADING

PRE-LOADING

(by volume)

Excess blood flows to the heart or to individual chambers:

• hypervolemia;
• reducing the capacity of the venous system;
• heart valve insufficiency

AFTER LOADING

(by resistance)

The heart or its individual departments are forced to work against:

- increased peripheral vascular resistance. In hypertension of the great circle of blood circulation, the overload of resistance falls on the left ventricle, and in hypertension of the small circle - the right ventricle;

- heart defects - stenosis of the valve openings

VOLUME OVERLOAD

• At insufficiency of aortic and mitral valves overload of a left ventricle develops.

​

​

• In case of insufficiency of the pulmonary artery valve and tricuspid valves - right ventricular overload.

OVERLOAD BY RESISTANCE

• In hypertension of the great circle of blood circulation, the overload of resistance falls on the left ventricle, and in hypertension of the small circle - the right ventricle.
• At a stenosis of an aortic opening overload of a left ventricle develops, at a stenosis of an opening of the mitral valve - the left auricle, at a stenosis of an opening of a pulmonary artery - a right ventricle, at a stenosis of an opening of the tricuspid valve - the right auricle.

HEART FAILURE �is a pathological condition caused by the inability of the heart to provide blood supply to organs and tissues in accordance with their needs.

�

PATHOGENESIS �OF HEART FAILURE

• Heart failure due to myocardial damage is characterized by a decrease in stress developed by the heart and manifested by a decrease in strength and speed of its contraction and relaxation
• Heart failure due to myocardial overload is formed against the background of a more or less long period of its hyperfunction, which in the end also leads to a decrease in the strength and speed of contraction and relaxation of the heart.

DISORDERS OF HEART FUNCTION AND HEMODYNAMICS IN HEART FAILURE

• REDUCTION of beat and minute emissions of heart;
• INCREASE of residual systolic blood volume (consequence of incomplete systole);
• INCREASE in end-diastolic pressure in the ventricles of the heart as a result of an increase in the amount of blood accumulating in their cavities, as well as impaired myocardial relaxation;
• DILATATION of heart cavities due to increase in them of end diastolic volume of blood and stretching of a myocardium;
• INCREASE of blood pressure in those regions of a vascular bed and cardiac cavities from where blood arrives in mainly affected department of heart;
• REDUCING the speed of the contractile process (increasing the duration of the period of isometric stress and systole in general).

MECHANISMS OF HEART FAILURE COMPENSATION

IMMEDIATE

(urgent)

• Heterometric compensation mechanism according to Frank-Starling law
• Homeometric mechanism
• Tachycardia

REMOTE

(deferred)

Myocardial hypertrophy - an increase in myocardial mass due to an increase in myocardial cell volume is aimed at performing increased work without a significant increase in the load per unit muscle mass of the heart

FEATURES �OF HYPERTROPHIED MYOCARDIUM

• dysregulation due to the lag of growth of nerve endings from the increase in the mass of cardiocytes;
• decreased supply of myocardium by vessels due to the lag of growth of arterioles and capillaries from the increase in the size of muscle cells;
• increase in the mass of myocardial cells in comparison with their surface (as a consequence - the development of ionic imbalance and disruption of cell metabolism);
• decreased energy supply of myocardial cells due to the lag of mitochondrial mass compared to the mass of myofibrils;
• violation of plastic processes in cardiomyocytes as a result of a relative decrease in the number of mitochondria, the volume of the microcirculatory tract, etc.

Normal heart

Hypertrophied heart (diastolic heart failure)

Dilated heart (systolic heart failure)

STAGES �OF MYOCARDIAL HYPERTROPHY �(by F.Z. Meerson)

1. The emergency stage combines pathological changes in the myocardium with the mobilization of myocardial reserves. Myocardial mass increases by 30-60%. The intensity of functioning of structures (IFS) increases.
2. Stage of completion of hypertrophy and relatively persistent hyperfunction. Pathological changes in the myocardium disappear. Myocardial mass increases by 100-120%. IFS is normalized.
3. Stage of gradual exhaustion and cardiosclerosis. IFS is growing.

ANALOGIES WITH DONKEY�Cardiac overload and ventricular dysfunctions limit the patient's ability to perform normal activities in daily life

ANALOGIES WITH DONKEY�Reduce the number of bags on the cart! �Use diuretics and ACE inhibitors for �HEART TRANSHIPMENT

​

​

​

MYOCARDIAL DAMAGE

coronary

Coronary Heart Disease (CHD)

non-coronary

• Hypoxic necrosis
• Electrolyte-steroid cardiomyopathy
• Autoimmune damage

blood flow is blocked

clogged coronary artery

damaged myocardium

CORONARY HEART DISEASE

​

is a pathological condition characterized by absolute or relative disruption of myocardial blood supply due to damage to the coronary arteries of the heart. In case of coronary heart disease there is a violation of blood flow in the coronary vessels, which leads to insufficient blood supply to the heart muscle

REGULATION �OF CORONARY CIRCULATION

• Myogenic autoregulation according to Bayliss's law stretching of smooth muscles of vessels increases force of their reduction
• Metabolic regulation is carried out by a number of metabolites (hydrogen ions, potassium, lactic acid, prostaglandins). The most important is adenosine as a natural blocker of calcium channels, it reduces the flow of Ca2 + ions into the cytoplasm, resulting in a decrease in basal coronary tone and blood circulation improves
• Nervous regulation has an indirect effect, neurogenic tone of coronary vessels is insignificant

CLINICAL CLASSIFICATION

OF CORONARY HEART DISEASE

• Sudden coronary death
• Angina pectoris

Stable angina pectoris

Stable angina pectoris with angiographically intact vessels

Vasospastic angina

Unstable angina

• Acute myocardial infarction

Acute myocardial infarction with the presence of a pathological Q wave (transmural, large focal)

Acute myocardial infarction without pathological Q wave (small-focal)

Acute subendocardial myocardial infarction

Acute myocardial infarction (undetermined)

Recurrent myocardial infarction (3 to 28 days)

Recurrent myocardial infarction (after 28 days)

• Acute coronary insufficiency
• Cardiosclerosis
• Painless form of Coronary Heart Disease

FEATURES �OF CORONARY CIRCULATION

• High level of oxygen extraction in the capillaries of the heart (70-75%, due to the significant length of its capillaries and longer contact time of the blood with the capillary wall)
• High basal tone of coronary vessels (provides coronary circulation at the level of 250-300 ml / min, which is 5% of the Minute Blood Volume)
• Phase nature of coronary circulation subordination of coronary circulation to metabolic needs of heart (in the conditions of pathology this subordination is broken and sensitivity of coronary vessels to nervous impulses increases)
• High sensitivity of coronary vessels to a decrease in oxygen pressure in the blood (reduction of pH by 5% significantly increases the intensity of blood circulation)
• Insufficient development of collateral vessels (under adverse conditions, collaterals in the heart can not compensate for impaired blood flow in the coronary vessels)

​

INSUFFICIENCY �OF CORONARY CIRCULATION

Coronary insufficiency is a pathological condition characterized by the inability of coronary vessels to supply blood to the heart in accordance with its energy needs.

Types of coronary insufficiency

• Relative coronary insufficiency occurs in the case of the primary increase in the energy needs of the heart - an increase in the load on the heart during intense physical activity, hypertension
• Absolute coronary insufficiency occurs in the case of primary coronary circulation, resulting in reduced delivery of oxygen and myocardial nutrients both at rest and with increasing energy needs)

FACTORS THAT CAUSE �ABSOLUTE CORONARY INSUFFICIENCY

• Reduction of perfusion pressure - at the same time coronary insufficiency of the central origin, the causes of which are:
• arterial hypotension (at all types of shock, collapse, insufficiency of aortic valves) At decrease in BP mechanisms of myogenic regulation work, however when BP is below 70 mm of mercury, these mechanisms appear insufficient.
• venous outflow disorders (with decompensated right ventricular failure, when increasing central venous pressure and end-diastolic pressure)
• Increased resistance of coronary vessels - this develops coronary insufficiency of local origin, the causes of which are:
• increase in blood viscosity (change of its rheological properties at dehydration, DIC syndrome, polycythemia)
• reduction of vessel diameter (this is the main factor of absolute coronary insufficiency). It causes ischemia of the heart

​

MECHANISMS OF DEVELOPMENT �OF MYOCARDIAL ISCHEMIA

• Obturation mechanism - reducing the lumen of the coronary arteries. Its causes can be:

a) stenotic atherosclerosis (in 90% of cases);

b) coronary artery thrombosis (as a consequence of atherosclerosis);

c) coronary artery embolism;

d) coronary heart disease (inflammatory processes that occur in rheumatism, syphilis)

• Angiospastic mechanism - coronary vasospasm. Its causes can be:

a) excitation of α-adrenoreceptors on the background of blockade of b-adrenoreceptors;

b) vasopressin;

c) angiotensin II;

d) thromboxane A2;

e) hypocapnia;

f) endothelin (clinical form of angiospasm - Angina Pectoris)

• Compression mechanism - compression of coronary vessels. Maybe with tachycardia, sometimes the cause is scarring and tumors

PATHOGENETIC FACTORS AFFECTING THE MYOCARDIUM UNDER ISCHEMIA

• Hypoxia (develops due to decreased myocardial perfusion - circulatory hypoxia)
• Acidosis (develops as a result of accumulation of acidic metabolic products due to impaired blood flow and activation of glycolysis)
• Increased extracellular concentration of potassium ions (causes disruption of Na-K pumps and increased permeability of damaged membranes)

MYOCARDIAL ENERGY SUPPLY IN CONDITIONS OF HYPOXIA

• The maintenance of the contractile function of the heart is due to the conjugation of the processes of contraction and energy supply.
• More than 90% of ATP is formed by oxidative phosphorylation in mitochondria due to oxidation of fatty acids (normal).
• Under conditions of hypoxia, energy supply is mainly due to the oxidation of glucose. When using glucose per 1 moll of oxygen is formed by 14% more ATP than when using fatty acids.
• In addition to these energy substrates, cardiomyocytes can use auxiliary substrates: ketone bodies, lactate, amino acids.
• ATP energy is spent on:

1) on the tension of the actin head in myofibrils during contraction;

2) to work Ca pump in the sarcoplasmic reticulum;

3) for operation of the membrane Na-K pump;

4) for the operation of special K-channels, which, by attaching ATP molecules, are closed and thus serve to maintain the RMP.

ADAPTATION OF THE MYOCARDIUM TO THE CONDITIONS OF HYPOXIA

• Hibernated (sleeping) myocardium - a short-term state of myocardium caused by low perfusion, which partially (up to 20 min) or completely (up to 5 min) disappears with improved coronary blood supply, or reduced myocardial oxygen demand and aimed at conserving ATP resources in chronic forms of coronary heart disease.

​

• Formed (stunned) myocardium is a transient post-ischemic dysfunction of the left ventricle, which persists after reperfusion in the absence of irreversible changes in the myocardium and after the restoration of normal or almost normal blood flow.

REPERFUSION INJURIES OF THE FORMED MYOCARDIUM

• Reperfusion syndrome is a syndrome that occurs as a result of the resumption of blood circulation in the ischemic area of ​​the myocardium, as a result of reperfusion.
• Restoration of coronary circulation can be caused by: cessation of coronary angiospasm, thrombus lysis, destruction of blood cell aggregates, surgical removal of the thrombus.
• Clinical manifestations of reperfusion syndrome: increase in the intensity of myocardial damage immediately after the restoration of coronary circulation, as a result of which the patient's condition deteriorates sharply. If the duration of ischemia is less than 20 minutes, this syndrome does not develop (this duration is typical for angina attacks)

CARDIOMYOCYTE DAMAGE

• Damage to cardiomyocytes in ischemia is cytopathic (indirect) and occurs due to primary disorders of intracellular homeostasis.
• Damage can be:
• Calcium
• lipid (POL, activation of membrane phospholipases, detergent action of FFA)

3) acidotic

4) electron-osmotic

5) protein

6) nucleic

LIPID DAMAGE

Violation of barrier function of cardiomyocytes at activation of LPO:

Ionophoric mechanism (due to the appearance in the cell of substances having the properties of ionophores, i.e. compounds capable of facilitating the diffusion of ions through the membrane due to the formation of complexes passing through its layers. In this case, the permeability of cell membranes for these ions increases.

The mechanism of electrical breakdown (associated with the existence on the plasma and mitochondrial membrane of cardiomyocytes potential differences. As a result of the appearance of LPO products violate the insulating properties of the hydrophobic layer of cell membranes, which leads to an electrical breakdown of the membrane, i.e. to its electromechanical rupture with the formation of new transmembrane channels of ionic conductivity.

PROTEIN DAMAGE

• Inhibition of enzymes (reversible and irreversible)
• Denaturation (due to rupture of covalent bonds and changes in the secondary and tertiary structure of the protein)
• Proteolysis (performed under the action of lysosomal proteolytic enzymes - cathepsins and proteases, which are activated by Са²⁺ions)

NUCLEIC DAMAGE

• Disorders of DNA replication (DNA denaturation, damage to replication enzymes, triphosphonucleotide deficiency)
• Violation of transcription (mutational defects of mRNA, post-transcriptional modification of mRNA - non-attachment of the "cap", violation of the formation of poly-A tail, splicing disorders, etc.)
• Translation disorders (Deficiency of mRNA, tRNA, mRNA, ribosomic enzymes and non-enzymatic proteins, free Amino acids and ATP)

CONSEQUENCES OF MYOCARDIAL ISCHEMIA

• Impaired myocardial contractility with the development of heart failure.
• The appearance of abnormal electrical activity - electrical instability of the heart, the development of arrhythmias.
• Damage to cardiomyocytes due to hypoxia.
• Reperfusion syndrome.

THANK YOU FOR ATTENTION