Pathophysiology of cardiovascular system
.pdfPathophysiology of cardiovascular system (The questions to the colloquium)
1.What does it mean: Heart failure? What are the pathogenetic mechanisms of heart failure?
HF- is a state of reduced myocardial performance when the heart can no longer works adequately as a pump: to throw out appropriate blood volume(SV, CO) and/or to move it against BP in vessels. (any functional or structural disorder of the heart)
Mechanism:
1)primary myocardial injury(decrease contractility, loss of muscle) [postischemic cardiosclerosis, myocarditises (infectious, allergic, autoimmune, toxic – e.g. due to alcohol), cardiomyopathies, cardiomyodystrophy..]
2)HF as a result of intensive work and exhaustion(Volume overload, pressure overload or both)
3)HF due severe arrhythmia (AV blockade, paroxysmal tachycardia, fibrillation)
2.What does it mean – Cardio-vascular failure? Name 3 pathogenetic
mechanisms of cardio-vascular failure.
CV failure means that CV system can’t provide tissues with a steady supply of vital nutrients and O2 and facilitate the excretion of waste products.
Mechanisms: 1. Decrease in total blood volume; 2. Heart diseases (pump dysfunction); 3. Vessels diseases.
3. What does it mean: Cardiac insufficiency ? Name the forms of cardiac insufficiency.
Cardiac insufficiency is when the heart muscle's pump function is reduced. This leads to the heart being unable to produce the power to pump the required amount of blood throughout the body.
Types: acute and chronic insuff, compensated (latent) and decompensated (obvious) insuff, cardiac/ vascular/ mixed forms.
•Right-sided heart failure. (Back-ups in the area that collects "used" blood)
•Left-sided heart failure. (Failure to properly pump out blood to the body)
•Congestive heart failure. (Fluid backs up into the lungs and tissues)
4.Write causes (diseases, conditions) which can lead to chronic “left/sided” heart overload by high volume.
Regurgitant valves, high venous return (veins contraction, physical activity, incr blood amount from muscles), incr blood volume (secondary aldosteronism as a result of RAAS activation, polycytemia (Wakesa d.))
??? Insufficiency of valves, hypervolemia due to chronic renal insufficiency, secondary aldosteronism (Iscenko Cushing)
5. Write causes (diseases, conditions) which can lead to chronic “left/sided” heart overload by high pressure.
Arterial hypertension, secondary (symptomatic) arterial hypertension, atherosclerosis of aorta, aortal valve stenosis
6.Write causes (diseases, conditions) which can lead to chronic “right/sided” heart overload by high pressure.
Aortal ostium stenosis, chronic obstructive lung disease, mitral valve stenosis, pulmonary hypertension
7.Write causes (diseases, conditions)which can lead to acute “left/sided” heart failure.
Trauma (blood loss)&shock, myocardial infarction, hypertensive crisis (high AP) (in base of hypertonic disease, pheochromocytoma, Conn syndrome), acute myocarditis (toxic or infectious), formation or decompensation of some heart valve diseases, severe arrhythmias (eg. Ventricular fibrillation), pericardial tamponade
8. Write causes (diseases, conditions) which can lead to acute “right/sided” heart failure.
Massive embolism of the pulmonary artery or its branches by thrombi from the veins of the systemic circulation or the “right heart”, respiratory distress syndrome of adults.
Right ventricle infarction, decompensation of chronic right ventricle failure, massive pleuritis, status astmaticus.
9. Enumerate the diseases and conditions which can lead to chronic right heart insufficiency.
Chronic obstructive lung disease, pulmonary hypertension, right ventricle valves disease, ischemic heart diseases, hypoxia-induced vasoconstriction, congenital shunts, mitral valve stenosis, aortic ostium stenosis, MI, chronic hypoxemia
11.What ion has a direct relation to a (heart) muscle contraction? Calcium
12.What formulas can be used for calculation of stroke volume, ejection fraction, heart index, cardiac output?
SV=EDV-ESV; EF=SV/EDV; HI=CO/body area, CO=SV*HR
13.Which of the cardiac indices (1) must be used for best quantitative evaluation of pumping heart work?
EDV, ESV, SV, EF, EDP
14. Enumerate acute (4) and delay (1) intracardiac compensatory mechanisms in patient with heart failure.
1) Frank-Starling relationship (when high preload); 2) Homeometric mechanism (when high afterload) = Anrep effect; 3) inotropic effect of high HR; 4) inotropic effect of sympathetic NS
Delay: + hypertrophy (physiological or pathological)
15. Describe the “Starling” low.
The increase of force of contraction that accompanies the increase in ventricular EDV. The anatomic arrangement of actin and myosin filaments in myocard is such that the force of contraction is greater when muscle fibres are optimally stretched just before they begin to contract. Max force = 2.5 times stretching normal resting length. Incr EDV = incr SV
16.How does the stroke volume (or heart work) change when Starling curve shifts to the right (or to the left)?
Shift to right and down – lower SV (incr afterload or decr inotropy) Shift to left and up – greater SV (decr afterload or incr inotropy)
17.What is the best mechanism for compensation for chronic heart insufficiency? The compensatory mechanisms that have been described thus far include: activation of the sympathetic (adrenergic) nervous system (SNS) and renin–
angiotensin–aldosterone system (RAAS), which maintain cardiac output through increased retention of salt and water, peripheral arterial vasoconstriction.
18. Point out the main compensatory mechanisms (heartand non-heart) of decreased CO in patient with heart failure.
Heart: 1. Heterometric (Frank-Starling) if incr preload
2.Homeometric – if incr afterload
3.inotropic effect of high HR (incr contraction force due to incr income Ca in plato phase)
4.inotropic positive catecholamines effect (due to betta1 adrenoR -> incr income
Ca)
Non-heart: activation of RAAS, symp NS
19. Describe the mechanisms (3) of tachycardia in case of heart failure.
Decr in SV, CO, AP causes excitation of lateral divisions of vasomotor center by baroreceptors of aortic arch and carotid sinus ( high pressure R) -> symp nerves transmit excitation to the heart -> HR incr
Irritation of chemoR of these zones (decr PO2, pH and incr Pco2) -> symp nerves - > incr HR
Incr pressure in right atrium due to reduced pumping function of RV -> tachycardia (Bainbridge reflex: distention of RA -> stimulation of atrial stretch R (low pressure baroR) -> n.vagus -> medulla obl-> inhibit posterior nucleus of n.vagus -> cause excitation of lateral divisions of vasomotor center -> symp n -> incr HR
20. Name the trigger factors which lead to pathologic hypertrophy of the heart. 1)increase in hemodynamic overload = incr in mechanical work, incr preload, afterload or heart rate
2)genetic factors (defects of membrane channels, hormones)
3)influence of neurohumoral factors on the myocard – sympathetic NS, epinephrine, AT2, aldosteron, GH, different growth factors
4)influence of some cytokines: IL1, TNF, IFgamma: cause production of induced
NOsynthase that have toxic action on myocard, stimulate apoptosis and fibrosis.
21. Enumerate the pathogenetic mechanisms that take part in development of pathological hypertrophy.
Causes as the trigger factors activate cell’s protooncogenes -> myocytes synthesized growth’s factors and receptors to them, intracellular transporters and proteins which regulate genes transduction -> incr number of myofibrils -> pathological hypertrophy due to activation of fetal program with negative features for an adult organism.
22.Name the three successive stages of cardiac pathological hypertrophy.
1.emergency or the stage of acute hemodynamic load
2.stage of stable hypertrophy or resistance
3.stage of decompensation or progressive cadriosclerosis
23.How and why change the heart reserve at pathological hypertrophy. Decrease – result of unbalanced growth of muscle tissue.
Mass of myocardium grows faster than axons of sympathetic neurons innervating them, density of symp innervations decr, expenditure of norepinephrine exceeds
its resynthesis -> controllability of heart, positive inotropic effect and relaxing effect og symp NS decr.
Growth of arterioles anf capillaries lags behind (if incr load ->ischemia -> coronary heart disease, MI)
Cell mass incr more than its surface
Mass of mitochondria is insuff for the incr mass of heart muscle -> energy potential of cells decr.
Myosin with low ATPase capacity is synthesized -> velocity of contraction decr.
24. What are the features of alarm stage of the heart hypertrophy?
Starts immediately after action of damaging factor on heart. Unexpected load -> compensation with intra and extracardial urgent, immediate mechanisms -> death or clinical signs and symptoms of acute HF and start of development of pathological hypertrophy. (incr HR, activation of symp NS, Frank-Starling mech activation, RAAS activation to incr blood volume)
25. Give the characteristics and features of third stage of heart hypertrophy. Stage of decompensation of the heart due to progressive cardiosclerosis (decr CO -> dilation of heart chambers, death of cardiomyocytes -> decr wall thickness and tension in wall incr.)
26. What are positive and negative effects of left ventricle hypertrophy in patient with chronic heart failure?
Pros: ventr wall thickness incr -> incr force of contraction, incr T and O2 demand. Cons: nerves, vessels, organelles and myofibrilles growth imbalance -> bad regulation, weak + inotropic effect of symp NS, decr cardiac reserve, incr relative surface membrane, incr anabolic processes, intracellular Ca -> bad diastole -> cardiosclerosis -> heart failure.
27. Enumerate clinical symptoms of chronic heart failure.
-pale and cold skin; cyanosis, acrocyanosis; edemas, ascites, enlargement of liver and spleen due to blood congestion; dyspnea; tachycardia; decreased tolerance of physical exertion; remodeling of myocardium (pathological dilation of the heart cavities, chandes in their geometry (become spherical), pathological hypertrophy, sharp incr in tension of the heart walls, marked changes of the systolic and diastolic function).
28. Definition the tern “chronic heart failure”.
- is a complex clinical syndrome characterized by pathological changes of LV function and neurohumoral regulation. Is accompanied by low tolerance of physical exertion, fluid retention in organs and tissues and a decrease in life expectancy. (ongoing inability of the heart to pump enough blood through the body to ensure a sufficient supply of O2)
29. Name the main hemodynamic index characterizes systolic dysfunction at CHF. Decrease in EF (less than 0.4) and CI (less than 2.5 l/min/m2), increase ESV and EDV; for LV – increase in EDP and in pulmonary capillary wedge pressure. Also CO, SV, cardiac reserve, meanAP decr; AV difference of O2, pressure in large veins incr.
30.Name the hemodynamic indexes which characterize the systemic circulation. CO, cardiac reserve, cardiac index, arteriovenous difference by O2, utilization coefficient of O2, mean AP, pressure in large veins.
31.How does the level of Ca2+-ions change (¯-) in the hypertrophied cardiomyocytes?
Increase
32.How does the relative myocardial fiber surface change in the hypertrophied cardiomyocytes?
Decrease
33.How do cardiac index, venous pressure, peripheral vessel resistance,
aldosterone production change at congestive heart failure? CI decrease ( cause CO decrease) HI=CO/A
VP increase (из-за увелич постнагрузки ЛП при митральном стенозе, повышается давление в венах, далее жидкость выходит в окружающую ткань в легких)
TPVR increase из-за компенсаторных механизмов. Активируется симпатика,
NE
Aldosterone, скорее всего снижается, так как давление очень высокое в сосудах, раздражаются барорецепторы, следовательно, нужно меньше жидкости
34. Name the main neuro-hormonal systems (2) that are activated by chronic heart failure.
• Симпатика: contractility, HR, spasm of veins, arteries, renin => increase CO, AP, perfusion
• RAAS + ADH
35. Positive: increase of contractility, increased CO, AP, perfusion, increase venous returned, RAAS+ ADH secretion => increased blood volume => CO INCREASED, spasm of arteries => increased AP and perfusion
Negative: increase of HR, pre and after load, increase of O2 demand, decrease of intracardiac NE storage = decrease in response of catechismo ed due to downregulation of B1-adrenergic receptors, decrease of renal and gastrointestinal perfusion, decrease of duration of diastole and coronary blood flow
36. Describe the mechanism of sympathetic nervous system activation by congestive heart failure.
1)Decreased SV left leads to not stretching aortic baroreceptors leads to SNS activation
2)Decreased AP leads to not stretching aortic baroreceptors leads to SNS activation
3)Decreased pO2 Increased pCO2 Decreased pH leads to activation of chemo receptors leads to activation of SNS
37. Describe the mechanism of secondary aldosteronism by congestive heart failure.
Порядин: Вторичный альдостеронизм развивается в результате уменьшения кровотока через кору почек и в рез-те активация симпатической НС (клетки ЮГА имеют ẞ-ар). Ренин + ангиотензиноген 1 -> ангиотензин1 + АПФ -> ангиотензин2 -> секреция альдостерона -> Задержка Na почками-> секреция АДГ -> задержка воды почками =>↑ОЦК.
38. Enumerate negative effects of prolonged tachycardia Possible complications include:
•Blood clots that can cause a stroke or heart attack
•Inability of the heart to pump enough blood (heart failure)
•Frequent fainting spells (обмороки) or unconsciousness
•Sudden death, usually only associated with ventricular tachycardia or ventricular fibrillation
39. What are the complications of secondary aldosteronism ?
а) Натрий накапливается в организме в межклет жидкости и в стенке сосудов => в крови может произойти гипонатриемия ( отеки итд )
б) Гипокалиемия => угнетение сократительной функции сердца. При значительном дефиците К+ -некроз миофибрилл.
в) Увеличенный V крови увеличивает пред- и постнагрузку на поврежденное сердце, развиваются отеки, стимулируется ремоделирование миокарда.
* может привести к аритмии ( но если не спросятне говорим, в порядине нет)
г) ремоделирование миокарда
40. Enumerate positive and negative effects of activated RAAS during chronic heart failure.
Positive:
•Увеличивается венозный возврат к сердцу-> стимулируется механизм Франка-Старлинга-> увеличивается УД-> увеличивается МОС (cardiac output)- > увеличивается АД
•Увеличивается ОПСС в ответ на возросший ОЦК и воздействия на сосуды Натрия, нагиотензина 2 и АДГ-> увеличивается АД
Negative:
•Вследствие задержки Натрия происходит потеря Калия через почки с развитием ГИПОКАЛИЕМИИ-> угнетение сократительной функции сердца->
при значительном дефиците Калия – некроз миофибрилл
•Увеличенный объем крови увеличивает пред- и постнагрузку на поврежденное сердце, развиваются отеки, стимулируется ремоделирование миокарда.
•Ремоделирование миокарда
41. Explain the mechanism of lung edema when "wedge" pressure of pulmonary capillaries is equal to 30 mm Hg.
Начальное звено отекарезкое снижение насосной функции левого желудочка и увеличения в нем давления (КДД-end diastolic pressure) -> возрастает давление в ЛП, в легочных венах и на венозном конце легочных капилляров-> развивается транссудация, отек легких. Когда давление 30 мм рт ст отек становится макисмальным -> развитие приступа удушья, кашля, появляются клокочущее дыхание и обильная пенистая мокрота с примесью крови
42. Describe the atriopeptide role in mechanisms of chronic congestive heart failure development.
Основной ответ: При СН синтез НУФ увеличивается, что связывают с ухудшением прогноза заболевания, тк эффект их уменьшается. Это объясняют недостаточной «зрелостью» МНУФ, усилением гидролиза НУФ нейроэндокринной пептидазоймембранной металлопротеиназой 2 типа. Дополнение: При СН натрийуретический фактор выделяются кардиомиоцитами желудочков ( в норме в резте дилатации предсердий). Основной – МНУФ (мозговой НУФ), выделяется в форме прогормона. Функции НУФ в норме, на всякий случай: НУФ способствует усилению выведения натрия (в 30 раз) и воды (в 10 раз), уменьшает пред- и постнагрузку, расширяет периферические сосуды, снижают АД, секрецию ренина и альдостерона, активность симпатической нервной системы)
44. Describe a pathogenesis of cyanosis at heart insufficiency.
Decreased blood flow and increased time of oxygen absorption by the tissues. Decreased oxygenation of blood in congested lungs also plays a role.
45. Describe a pathogenesis of edema at heart insufficiency.
Increase of hydrostatic pressure on venous end of capillaries. Activation of RAAS and ADH leads to Na and water retention, increase in blood volume and fluid accumulation. ( + decreased albumin synthesis in the congestive liver and increased albumin loss by the kidneys leads to decrease of oncotic pressure => transudation.
46. Describe a pathogenesis of shortness of breath at heart insufficiency.
A rise in pulmonary capillary pressures as a consequence of elevated LV and LA pressures. Increased pressure on venous capillary end versus oncotic pressure => transudation.
Interstitial edema stimulates juxtacapillary receptors, causes reflex rapid and shallow breathing => dyspnea.
Edema of bronchial walls leads to small airway obstruction, wheezing (cardiac asthma).
Sudden onset of severe breathing at night – paroxysmal nocturnal dyspnea, due to decreased adrenergic support of ventricular work; increased blood return to the heart from the legs-preload; normal nocturnal depression of respiratory center.
47.Describe a pathogenesis of typical skin symptoms at heart insufficiency. Pale skin due to spasm of peripheral vessels and centralixation of blood flow as a result of activation of sympathetic NS.
Sweating because it is the only heat loss mechanism when there is spasm of vessels.
48.Mechanism of positive effect of use the ACE inhibitors in therapy of chronic
heart failure
ACE inhibitors decreased AT2, decrease aldosterone => decrease NA reabsorption => decrease ADH secretion => decrease water reabsorption => decrease blood volume => decrease venous return => decrease preload.
Decrease of TPVR => decreased afterload
Vasodilatating action due to blocking of bradykinin degradation, which increases NO synthesis.
Slow down myocardium remodeling.
Decreased aldosterone => increased K => no hypokalemia
49. Why did the venous return decrease after massive blood loss?
Blood loss leads to decrease of blood volume, which leads to decrease of venous return.
50.Write three main organ-targets to angiotensin. Heart, kidneys, vessels
51.Write main organ-targets to aldosterone. Kidney, blood vessels, ??liver, smooth muscle cells
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52. Why does the left ventricle more often involve in ischemic process?
Left ventricle contracts against the greater resistance and so it has higher oxygen demand
53.How much times must coronary flow increase in order to teach it maximum in comparison with normal at rest (coronary reserve)?
5-6 times. Basal flow= 225 ml, Max flow=1225ml
54.In what phase of cardiac work does coronary flow mostly occur?
Mainly during the diastole(85%), during the systole only 15%.
55. Name the factors which can decrease the coronary blood flow.
Spasm of coronary vessels, Stenotic atherosclerosis, Thrombosis of coronary vessels, Embolism of coronary vessels, decreased DAP
56. Enumerate the causes and conditions which provoke the ischemic heart disease.
Lack of oxygen that enters the heart muscle because of: 1. Spasm of blood vessels. 2. Stenotic atherosclerosis 3. Thrombosis of coronary vessels 4. Embolism of coronary vessels
57. Which causes can lead to Myocardial Infarction of left ventricle?
Spasm of coronary vessels, Stenotic atherosclerosis, Thrombosis of coronary vessels, Embolism of coronary vessels (thromboemboly from left heart при наруш тока крови)
58.Write the risk factors (5) of myocardial infarction.
Dislipidemia with increased amount of low and very low density lipoproteins, Arterial hypertension, Smoking, Diabetes mellitus, Stress, Heredity
59. What is the mechanism of lung edema in patient with acute myocardial infarction?
Development of left ventricle insufficiencyincrease final diastolic pressureincrease of pressure in left atrium, then in pulmonary veinsincrease of wedge pressure of pulmonary capillaries( more than 15)- transudation and formation of edema
60. What are the possible causes of arrhythmia development in Myocardial Infarction?
change in electrophysiological properties of myocardium in the area of damage
-appearance of ectopic areas, loose of electrical stability
-electrolyte disbalance in myocardium
-hypercateholaminemia (Myocardial infarction - stress reaction - increase Catecholamines - improving the need of myocardials in O2, increasing endothelin emissions, increase the aggregation of platelets and the synthesis of thrombooxane A2 = increased vasoconstriction and thrombotic activity - occlusion
of coronary arteries)
-acute dilatation of myocardium
-developing of re-entry phenomenon and high spontaneous diastolic polarization
61. The causes and role of pain sensation in pathogenesis of Myocardial Infarction Pain is stress for the body. The activation of sympatho-adrenal and hypothalamicpituitary and adrenal systems occurs
1) Activation of the sympathetic nervous system:
A) an increase in the needs of myocardium in oxygen -> risk raising even greater ischemia
b) heart rate -> shortening diastole -> Reducing the coronary blood flow