Pathophysiology_FULL

section: Laboratory diagnostics).

The subacute period is characterized by complete replacement of necrotic masses with granulation tissue and corresponds to the time of formation of a connective tissue scar at the site of the necrosis focus. With an uncomplicated course of myocardial infarction, the subacute period lasts from 6 to 8 weeks. The general condition of the patient is satisfactory, there is no pain syndrome. The study of the cardiovascular system reveals the normalization of heart rate, blood pressure, the disappearance of systolic murmur in the apex of the heart. In the subacute period, the manifestations of the resorption-necrotic syndrome disappear.

The postinfarction period (the period of postinfarction cardiosclerosis) corresponds to the period of complete consolidation of the scar in the necrosis focus and adaptation of the cardiovascular system to the new conditions of functioning - the exclusion of the contractile function of the myocardial area. This period continues throughout the rest of the patient's life. Allocate the nearest (2-6 months) and distant (after 6 months) postinfarction period. Most patients have no pain in the region of the heart. However, angina pectoris, which worried the patient before the development of myocardial infarction, often recurs in the future.

LABORATORY DIAGNOSTICS OF INFARCTIONAL INFARCTION

1. Data of laboratory research of peripheral blood:

neutrophilic leukocytosis with a shift of the leukocyte formula to the left, eosinopenia, lymphopenia, increased ESR.

2.Data of biochemical blood test:

- the content of C-reactive protein, haptoglobin, IL-1, TNF increases due to the development of APR - the glucose content increases (the sympathetic nervous system is activated and the adrenaline

content in the blood rises);

-metabolic acidosis develops (lactic acid and hydrogen ions accumulate in the blood);

-the content of fibrinogen increases, the prothrombin index increases, the clotting time decreases (the mechanisms of hemostasis are activated, the development of DIC syndrome is possible);

-hyperkalemia develops.

3.Determination of blood levels of biochemical markers of Cardiomyocytes. With myocardial infarction, a number of protein molecules enter the bloodstream from the necrosis focus

The first to increase is the level of myoglobin in the blood, which is the light chain of myosin. An increase in the content of myoglobin in the blood begins within 2 hours from the onset of necrosis; its maximum level is observed after 6–10 hours; the duration of the increase in the content of myoglobin in the blood is about 2 days. The specificity of determining a high level of myoglobin in the blood in MI is 77-95% in the first 6 hours. The level of myoglobin in the blood can increase in MI by 10-20 times.

The content of troponins T and I in the blood increases. It is extremely important that these

troponins are contained in the myocardium in isoforms, the structure of the molecules of which differs from the molecules of these proteins in skeletal and smooth muscles. In this regard, the determination of the content in the blood of only cardiac troponins T and I (using monoclonal antibodies) is a highly specific test for detecting myocardial necrosis (specificity is 90-100%).

The activity of total cretin phosphokinase and its isoenzymes increases. Three isoenzymes are

known: CPK-MM (muscle), CPK-MB (cardiac) and CPK-BB (cerebral). Increased blood levels of CPK-MB are considered highly specific for MI.

There is an increase in the activity in the blood of lactate dehydrogenase (LDH) and its isoforms.

Due to the lack of cardiospecificity of total LDH, preference should be given to determining the activity in the blood of the LDH-1 level, because the myocardium is rich in this enzyme.

The content of aspartate aminotransferase (AST) in the blood increases after 6-8 hours, the

maximum increase is observed after 24-36 hours, while during the period of maximum the level of activity of this enzyme exceeds the normal level by 4-20 times! Considering that the activity of AST also

increases in other diseases, in particular, in liver pathology, it is advisable to simultaneously determine the activity in the blood of AST and ALT (the content of which in the liver is much higher than in the myocardium) and to calculate the de Ritis coefficient (the ratio AST / ALT), which is normally 1.33. With MI, this coefficient exceeds the normal value.

PRINCIPLES OF PATHOGENETIC THERAPY FOR INFARCTION Myocardium

1. Relief of pain syndrome:

-Pain relief with narcotic analgesics.

-The method of ataralgesia

-the combined administration of analgesic and traquilizing agents (seduxen, relanium), which is used for intense pain syndrome, accompanied by pronounced excitement, a sense of fear, internal tension.

-Neuroleptanalgesia, which is the most effective method of pain relief in myocardial infarction. A combined intravenous administration of the analgesic fentanyl and the neuroleptic droperidol is used.

-Anesthesia with nitrous oxide, which is used for intolerance to neuroleptanalgesia and narcotic analgesics.

2.Appointment of nitrates, especially nitroglycerin, in order to expand the coronary vessels, which helps to relieve pain, as well as reduce preload due to venodilation.

3.Oxygen therapy. Oxygen inhalation is recommended for all patients with MI, especially for pain, cyanosis, shortness of breath, left ventricular failure, cardiogenic shock. Inhalation of humidified oxygen is more expedient.

4.Thrombolytic therapy to restore the main coronary blood flow. Due to the fact that in most cases the cause of the development of myocardial infarction is thrombosis of the coronary artery affected by the atherosclerotic process, thrombolytic therapy carried out in the first 6 hours (before clot consolidation) is indicated for all patients with myocardial infarction.

5.Prevention of thrombus formation. For this purpose, anticoagulants (heparin, hirudin) and antiplatelet agents (aspirin, ticlopidine) are prescribed.

6.Decrease in myocardial oxygen demand:- a decrease in the tension of the ventricular wall ( •• adrenergic blockers, nitrates);- a decrease in the number and strength of heart contractions ( •• adrenergic blockers);- lowering the preand afterload in order to reduce the work produced by the heart (ACE inhibitors and vasodilators).

7.Limiting the size of myocardial infarction, which is achieved by early revascularization using thrombolytic

9. Treatment with metabolic cardioprotectors, which improve metabolic processes in the myocardium, help to reduce the

ischemic zone in myocardial infarction, and improve the functional state of the myocardium

48. Early and late complications of myocardial infarction. Biochemical blood indexes and the hemodynamic disturbances which characterize the myocardial infarction. Possible methods of therapy.

Early complications: arrhythmias, acute left ventricular failure with the development of pulmonary edema, cardiogenic shock.

1.Cardiogenic shock - extreme degree of left ventricular failure, characterized by a sharp decrease in the contractile function of the myocardium. Cardiogenic shock develops in about 20% of patients with MI. The following forms of cardiogenic shock are distinguished: reflex; true cardiogenic; areactive; arrhythmic; due to myocardial rupture.

True cardiogenic shock, as a rule, develops with extensive transmural myocardial infarction, with

the size of the necrosis zone equal to or exceeding 40% of the mass of the left ventricular myocardium. The main pathogenetic factor is a decrease in the contractile function of the myocardium. The process of myocardial remodeling plays an important role in reducing the contractile function of the myocardium. With cardiogenic shock, a vicious circle develops, which aggravates the course of this formidable complication. This mechanism begins with a sharp decrease of the systolic and diastolic functions of the left ventricular myocardium. A pronounced drop in stroke volume leads to a decrease in pressure in the aorta and a decrease in coronary perfusion pressure and, consequently, to a decrease in coronary blood flow, which further disrupts myocardial function.

2.acute left ventricular failure-

The factor is a decrease in contractility (systolic dysfunction) and a decrease in compliance (diastolic dysfunction) of the left ventricular myocardium, which leads to an increase in pressure in the left atrium, and then in the vessels of the pulmonary circle. In response to an increase in pressure in the left atrium, pulmonary arterioles spasm (Kitaev's reflex), which initially protects the small circle from overflow to a certain extent, and subsequently aggravates hypertension in the vessels of the lungs. When the hydrostatic pressure in the pulmonary capillaries begins to exceed the colloid-osmotic pressure, plasma sweating and fluid accumulation occurs first in the interstitium of the lungs and then in the alveoli. Pulmonary edema occurs.

3. Arrhythmias-

Cardiac arrhythmias and conduction disorders are an almost permanent complication

of large-focal MI. The main mechanisms of the development of arrhythmias in patients with MI are: a) changes in the electrophysiological properties of the myocardium in the affected area; b) electrical inhomogeneity of the myocardium; c) the appearance of ectopic foci, loss of electrical stability; d) electrolyte imbalance in the myocardium (loss of potassium, magnesium by cardiomyocytes, increased levels of potassium in the extracellular environment); e) hypercatecholaminemia; f) acute myocardial dilatation; g) development of the re-entry phenomenon and high spontaneous diastolic polarization. Single cycles of ectopic excitation or circular wave lead to extrasystole; a long period of activity of an ectopic focus or circulation of a circular wave through the myocardium lead to the development of paroxysmal tachycardia

The development of atrial fibrillation (especially of the tachysystolic form) has a serious prognostic value, which, due to the deterioration of coronary blood flow with shortening of diastole, aggravates the impairment of myocardial contractility; in addition, as a result of a decrease in the contribution of the left

atrium to the diastolic filling of the left ventricle, cardiac output is further reduced. The most dangerous is early ventricular fibrillation (chaotic twitching of individual myocardial fibers, lack of coordinated ventricular contraction), which is the main cause of death in patients with MI.

Late complications:

1.Formation of an aneurysm of the heart (occurs in 12-15% of transmural MI).

2.Heart ruptures: external, interventricular septum; detachment of the papillary muscle with the development of mitral valve insufficiency.

3.Thromboembolism, which develops in about 1/10 of those who have had myocardial infarction (the first place is

taken by pulmonary embolism - pulmonary embolism).

4. Postinfarction autoimmune Dressler syndrome. Myocardial necrosis, as well as changes in the peri-infarction zone, lead to the appearance of cardiac autoantigens, followed by the formation of autoantibodies that increase myocardial damage. This syndrome develops in approximately 3-4% of patients 2-8 weeks after the onset of myocardial infarction.

LABORATORY DIAGNOSTICS OF INFARCTIONAL INFARCTION

1. Data of laboratory research of peripheral blood:

neutrophilic leukocytosis with a shift of the leukocyte formula to the left, eosinopenia, lymphopenia, increased

ESR.

2.Data of biochemical blood test:

- the content of C-reactive protein, haptoglobin, IL-1, TNF increases due to the development of APR - the glucose content increases (the sympathetic nervous system is activated and the adrenaline

content in the blood rises);

-metabolic acidosis develops (lactic acid and hydrogen ions accumulate in the blood);

-the content of fibrinogen increases, the prothrombin index increases, the clotting time decreases (the mechanisms of hemostasis are activated, the development of DIC syndrome is possible);

-hyperkalemia develops.

3.Determination of blood levels of biochemical markers of Cardiomyocytes. With myocardial infarction, a number of protein molecules enter the bloodstream from the necrosis focus

The first to increase is the level of myoglobin in the blood, which is the light chain of myosin. An increase in the content of myoglobin in the blood begins within 2 hours from the onset of necrosis; its maximum level is observed after 6–10 hours; the duration of the increase in the content of myoglobin in the blood is about 2 days. The specificity of determining a high level of myoglobin in the blood in MI is 77-95% in the first 6 hours. The level of myoglobin in the blood can increase in MI by 10-20 times.

The content of troponins T and I in the blood increases. It is extremely important that these

troponins are contained in the myocardium in isoforms, the structure of the molecules of which differs from the molecules of these proteins in skeletal and smooth muscles. In this regard, the determination of the content in the blood of only cardiac troponins T and I (using monoclonal antibodies) is a highly specific test for detecting myocardial necrosis (specificity is 90-100%).

The activity of total cretin phosphokinase and its isoenzymes increases. Three isoenzymes are known: CPK-MM (muscle), CPK-MB (cardiac) and CPK-BB (cerebral). Increased blood levels of CPK-MB are considered highly specific for MI.

There is an increase in the activity in the blood of lactate dehydrogenase (LDH) and its isoforms.

Due to the lack of cardiospecificity of total LDH, preference should be given to determining the activity in the blood of the LDH-1 level, because the myocardium is rich in this enzyme.

The content of aspartate aminotransferase (AST) in the blood increases after 6-8 hours, the

maximum increase is observed after 24-36 hours, while during the period of maximum the level of activity of this enzyme exceeds the normal level by 4-20 times! Considering that the activity of AST also

3) Ischemia zone - coronary (equilateral and pointed) T wave (high positive for subendocardial MI, and negative - with sub-epicardial or transmural MI).

repolarization from epicardium to endocardium

repolarization from endocardium to epicardium

mechanism of formation of a negative coronary T wave.

ischemia will be subepicardial here. in the ischemic zone, the process of restoring the initial potential willbegin with a delay, therefore, the repolarization wave goes from the endocardium to the epicardium, and thevector is oriented towards the negative pole of the leads and a negative coronary tooth is recorded,

mechanism of formation of a positive coronary T wave.

ischemia is localized in the subendocardial regions. the repolarization wave moves from theepicardium to the endocardium, therefore the vector is directed to the positive pole, hence the

positive tooth.

Bright big amplitude, symmetric, sharp apex, T-wave <19mins,cell restore and survive, normal condition if more than 19min- ISCHEMIC INJURY

Acute stage characterized by fast, within 1 - 2 days, formation of a pathological tooth Q or complex QS, segment displacement RS — T above the isoline and merging with it at first a positive, and then a negative T wave. After a few days, the segment RS-T approaches the isoline, and at the 2nd week of the disease becomes isoelectric.

A negative coronary T wave deepens sharply and becomes symmetrical and pointed (reinversion of the T wave)

In subacute stage MI, a pathological Q wave or QS complex (necrosis) and a negative coronary T wave (ischemia) are recorded, the amplitude of which, starting from 20 —25- x days of myocardial infarction, gradually decreases. Segment RS — T located on the isoline.

Cicatricial stage MI is characterized by the persistence of a pathological Q wave or QS complex for many years and the presence of a weakly negative, smoothed, or positive T wave.

50. Secondary hypertensions. Clinical variants and mechanisms of their development.

Symptomatic or secondary hypertensions: The causes of symptomatic hypertension are primary diseases of various organs leading to high blood pressure.

1.Renal

2.Endocrine

3. Cardiovascular 4.Neurogenic

●Renal hypertension (about 14%) develops in diseases of renal vessels (vasorenal) or renal parenchyma (renoprival). It is conditioned mainly by activation of RAAS.

●Endocrine hypertension (about 3%) accompanies thyreotoxicosis, Conn’s syndrome, Itsenko-Cushing syndrome, pheochromocytoma. It is conditioned by overproduction of hormones.

●Cardiovascular hypertension (about 1.5%) develops in insufficiency of the aortic valve, hyperkinetic variant of the heart work with increased CO, coarctation of the aorta).

●Neurogenic hypertension (about 0.8%) is caused by organic lesions of the brain structures regulating BP (tumors, inflammation, injuries, concussion, cerebral hemorrhage).

51. Bronchial asthma. Classification. The mechanisms of the main clinical manifestations. Clinical complications in the patients with bronchial asthma.

Bronchial asthma - chronic inflammatory disease of lower airways. Types of bronchial asthma: Atopic(allergic) asthma, Non-atopic asthma, Aspirin-induced asthma, Exercise-induced asthma, coughing asthma.

Main clinical manifestations are: shortness of breath, wheezing, sometimes may appear cyanosis, and usage of accessory muscles(sternocleidomastoid).

Shortness of breath - in case of bronchial asthma patient has expiratory dyspnoe. Dyspnoe is a subjective feel of lack of air, that is formed in hypocamp, because of constant irritation of

different receptors( baroreceptors in aortic and carotid bodies, central chemoreceptors, stretch receptors in smooth muscles of airways, respiratory muscle fibers receptors)

Wheezing appears as a result of small airway obstruction

Cyanosis appears as a result of decreased oxygen concentration in the blood

Obstruction of airways(bronchi) in asthma is reversible process, but without any treatment that inflammation of airways may lead to airways remodeling and irreversible obstruction. Treatment: bronchodilators, eliminate allergen, allergen specific immune therapy, antiinflammatory drugs, membrane stabilizers of mast cells

52. Obstructive lung diseases. The clinical examples. The most important clinical symptoms and ventilation indexes that are characteristic of these diseases.

Obstructive diseasespathology of external breathing, in which resistance to the air flow is increased. Examples are: bronchial asthma, chronic obstructive pulmonary disease, tumor of upper airways, bronchiectasis, laringospasm, infection of upper airways.

Clinical symptoms of obstructive diseases are: dyspnoe (expiratory or inspiratory), stridor(upper) or wheezing(lower), cough, cyanosis.

Indexes: decreased FEV1, decreased Tiffnoe, decreased RR(resp reserve), increased residual volume (RV), increased TLC

53. Restrictive lung diseases Pathogenesis. Indexes of ventilation in this pathology.

Restrictive lung diseasespathology, in which gas exchange area is decreased.

Restrictive disorders could be extrapulmonary ( pathological changes in respiratory muscles such as disorders of innervation, decreased contractility in myasthenia, dystrophy; pathological changes in integrity of pleural cavity leading to limitations of excursion and open of alveoli such as pneumothorax, hydrothorax; impaired central control of ventilation such as overdose, encephalopathies, hematoma, tumor of the brain, traumas of spine or skull)

Restrictive disorders could be intrapulmonary ( all types of fibrosispneumosclerosis, pneumofibrosis; focal changestumors, atelectasis, pneumonia: lung edema; decreased activity of surfactant)

Indexes: decreased VC,decreased FVC, decreased TV, increased BR, norm Tiffeneau,

54. Pathogensis of impaired ventilation The causes and specific spirogramm indexes which characterize restrictive disturbance of ventilation.

Disorders of ventilation could be divided into obstructive, restrictive, combined and impaired control of ventilation.

55. Pulmonary edema The most important causes and the mechanism of outstanding. Acute complications and methods of treatment.

Pathological condition with fluid accumulation in the tissue and air spaces( interstitial and alveolar). Pulmonary edema leads to impaired gas exchange and further respiratory failure. Could be cardiogenic or noncardiogenic

Cardiogenic edemacould be as a result of left heart failure, when decreased CO leads to increased EDV and EDP in left ventricle, then it leads to increased EDP in left atrium and increased wedge pressure in pulmonary capillaries. Increased wedge pressure higher than 15 leads to interstitial edema, higher than 30 to alveolar edema. Increased fluid flow(higher than 0.6ml/min ) leads to overload and insufficiency of lymph flow > mixed respiratory insufficiency Non-cardiogenic edemadecreased oncotic pressure leads to massive fluid filtration to the interstitial tissue

Increased vascular permeability and further edema is called Respiratoty Distress-Syndrome. Because of increased permeability ( fast x2) massive protein leakage into the interstitial is occurred that leads to raise in oncotic pressure in interstitial and fluid filtration( wedge pressure is less than 18)

Complications: cardiogenic shock, blockage of resp. Tracts, ischemic injuries,

Treatment: mechanical ventilation, supplementary oxygen, in cardiogenic edema diuretics, inhibitors of ACE, analgesia(morphin), decrease pressure in pulmonary circulation by sitting position, tourniquets on hips, drugs that decrease vascular permeability.

56. Acute respiratory syndrome in the adults and newborns. The main causes and mechanism of development.

ARDSacute inflammation in alveolar wall with damage of alveolar -capillary membrane, characterized by acute onset, stable hypoxemia and cyanosis with lack of reaction on oxygen therapy, interstitial edema.

Causes: Direct lung injury( pneumonia, aspiration of gastric content, inhalation injury, trauma, burns)

Indirect lung injury( sepsis, severe trauma with shock and multiple transfusions, drug overdose) Pathogenesis: acute injury leads to release of IL1 and TNF >influx of inflammatory cells to the lung( neutrophils, macrophages, platelets)>release of radicals, cytokines, activation of complement system>increased permeability of capillaries and migration of proteins into interstitial >fluid filtration becouse of increased oncotic pressure and formation of pulmanary edema(noncardiogenic), damage to alveolocytes leads to decreased secretion of surfactant and decreased compliance> > right to left shunt, fibrosis, hyaline membrane formation> acute resp failure(mixed: disorders of ventilation, diffusion, perfusion)

ARDS of newborns

Causes:In newborns oxygen demand are higher, but alveoli amount are much lesser than in adult Pathogenesis: during birth all the liquid should be pushed out from the lungs and surface tension of fallen alveoli is high> resistance during inhalation>inadequate alveolar ventilation and hypoxemia, hypercapnia, ischemia of pulmanary parenchyma> injury of capillaries and alveoli>increased permeability and further edema>respiratory failure

57. Peptic ulcer disease The most important factors which are involved in this pathology and life-threatening complications. Methods of therapy.

Is a chronic intermittent and recurrent disease with a defect in the mucosa and may extend to submucosa or deeper.

PUD appears as a result of disbalance between protective and damaging factors(|exogenous and endogenous)

Ulcerogenic factors(exo):

Nutrition- irregular eating or prolonged starvation> fasting hypersecretion; spicy food, juices, coffee, beer, wine>gastric juice hypersecrition; lack of food>bad gastric juice absorption and neutralization

Bad habits- smoking( decreased blood flow, bicarbonate secretion and prgl E synthesis and regeneration of mucosa, increased HCl synthesis); Alcohol(increased HCl and gastrin secretion, direct damage of mucosa in large quantities)

H. Pylory- has enzyme urease that produce NH3 from urea and protects them from HCl, has enzyme catalaze that protects them from phagocytes. H. pylori secrets toxic lypases, proteases, phospholipases, produce ROS that destroy mucus and then membrane, stimulate secretion of IL1, IL6TNF

Drugs- NSAID(decrease Prgl synthesis, bicorbonate secretion, mucus formation);Catecholamines( vascular spasm and ischemia); Glucocorticoids( increase HCl secretion, decrease mucus formation and regeneration)

Stress- irritation of hypothalamus> increased tone of Vagus(increased HCl and pepsin formation, decreased mucus formation and motordisfunction)

Ulcerogenic factors(endo):

Acid-peptic factor- increased amount of histamine> increased HCl secretion; gastrin both increases HCl and pepsin secretion and improves regeneration and mucus formation, but in case of overproduction> too much HCl> ulcers

types: >normal\hyperchlorhydremic\hyperpepsinogenic\pyloric(both a lot) \hypochlorohydremic\hypopepsinogenic\achylic(both a little)

Motor disfunction- increased motility of stomach>acid component in duodenum>ulcer; decresed motility of stomach>long contact of acid with mucosa>ulcer; reflux>bile acids in stomach remove mucus and damage epithelium>ulcer, may also lead to cell metaplasia. Protective factors:

Mucosa- product mucus, keep H in the lumen by tight junctions, product bicorbonate, Prgl E, high ability to regeneration, intense blood flow, many mast cells regulate blood flow, Antro-