Physiopathology I Fall 2021 PDF

Université Libanaise - Faculté d’agronomie Et de médecine Vétérinaire Physiopathology I Dr. Rana CHAAYA Fall 2021 1  References For Animal Pathophysiology 1. Pathol...

Université Libanaise - Faculté d’agronomie Et de médecine Vétérinaire Physiopathology I Dr. Rana CHAAYA Fall 2021 1  References For Animal Pathophysiology 1. Pathologic Basis of Veterinary Disease, 5e, James F. Zachary DVM PhD (Editor), M. Donald McGavin MVSc PhD FACVSc 2.Essentials of pathophysiology. Carol Mattson Porth 3rd edition ,wolters kluwer 2 References For Animal Pathophysiology 3  Pathophysiology I: Pathology of Organ Systems 1. Cardiovascular Diseases 2. Respiratory Diseases 3. Nervous Diseases 4. The Urinary Diseases 4  Part 1: Cardiovascular Diseases Chapter 1 - Dysfunction/Responses to Injury Chap 2 - Congenital Heart Defects Chap 3- Endocardial and valvular disorders Chap 4 -Disorders of the Pericardium & Cardiomyopathies Dr CHAAYA Rana Fall 2021 Chapter 1 Dysfunction and responses to injury 6 cranial 7 7  Cardiac Anatomy The heart wall consists of three layers Serous membrane 1.The epicardium: an outer serous covering (visceral pericardium) 2.The myocardium is the thickest part of the heart wall and is made up of cardiac muscle. When cardiac muscle fibers contract, the heart beats. 3.The inner endocardium includes an endothelium formed from simple Continuous with squamous epithelium that lines the heart & lines the blood vessels. blood vessels visceral: attatched to the organ parietal: li fo2 l visceral w la barra aktar 8  What is Heart Disease? Cardiovascular disease is any condition of the heart or blood vessels that disrupts the normal function of the heart and vasculature to deliver oxygenated blood to the body. Heart diseases can be congenital (i.e. present from birth) or acquired (i.e. occur later in life). Many heart diseases in animals are heritable (passed on through generations). Often, heritable heart diseases occur with a higher prevalence in certain breeds of animals. 9 1.Dysfunction/Responses to Injury Dysfunction: Heart Failure:Pathophysiology of Heart Failure Heart failure is a progressive clinical syndrome in which impaired pumping decreases ventricular ejection and venous return. ya heart battal 3emil pump ya ma aam yousallo dam aw both sawa The heart fails either by decreased blood pumping into the aorta and/or pulmonary artery to maintain arterial pressure (low-output heart failure) or by ma aam e2dar talli3 dam an inability to adequately empty the venous reservoirs (congestive heart ma aam yousal enough blood failure: next slide). mn veins Signs of low cardiac output include lethargy, syncope, and hypotension, and those of congestion include ascites, pleural effusion, and pulmonary edema. failure huwe ekher stage bas actually hiye progressive msh faj2a btsir  Syndromes of Cardiac Failure or Decompensation: Congestive Heart Failure (CHF) CHF can be right-sided, left-sided, or bilateral and can occur with cardiac dilation and/or hypertrophy. bl right: l veines caves b jam3o blood=> acites, abdominal oedema bl left=> pulmonary vein ma aam b wasil blood=> blood b dal bl vein=> pleural oedema Right-sided CHF is associated with signs of congestion in the systemic circulation (i.e., ascites and peripheral edema ), whereas left-sided CHF causes fluid jouwa l lungs signs of congestion in the pulmonary circulation (i.e., pulmonary edema and dyspnea). In small animals, pleural effusion is usually associated with bilateral 7wela l lungs w hon usually fina neshabun mn l maylteyn fi congestive heart failure. mchkle bl vein return Heart failure may result from an inability of the heart to eject blood adequately (systolic failure), from inadequate ventricular filling (diastolic adey bytla3 dam mn l ventricle/beat failure), or both. The resultant reduction in stroke volume (SV) leads to a decrease in cardiac output (CO) and a decrease in arterial blood pressure. dilated hypertrophy Ascites, Congestive Heart Failure, Furazolidone Cardiotoxicity, Heart and Liver, Duckling. Note prominent accumulations of serous fluid in the coelomic cavity and fibrin deposits over the surface of the liver. The heart (H) is dilated. bl normal LV thick aktar mn right  Cardiac Output Blood is forced out of the ventricles with each heartbeat. syst nerveux sympathique increases heart rate parasymp b allil l heart rate The Stroke Volume is the volume of blood pumped by one ventricle with each beat (L/beat) The Cardiac Output is the volume of blood pumped by each ventricle per minute (L/min) sympathetic Increases in HR increase CO linearly until a plateau is reached, at which point increases in HR will decrease CO because of decreased diastolic filling. ma b la7i2 y3ml relaxation la y3abbee dam 15  afterload hiye mtl resistance y3ne eza Regulation Of Stroke Volume 3nna stenose matlan y3ne ma fiyo ytla3 kel l volume, aw valve manzou3 => decrease l afterload=> stroke volume b zid le2n ma3sh fi resistance The heart will pump all the blood returning during systole. m3alla2a bl pressure bas myocardiocytes adey heart bado y3ml pump Three factors regulate stroke volume:amount Preload, Contractility, and Afterload. 3m yshteghlo of blood bl heart abl contraction SV increases with increases in preload and contractility and decreases in afterload. Preload reflects the degree of ventricular filling just before contraction. End diastolic volume (EDV) can estimate preload. The amount of blood in the ventricles just before systole is the end-diastolic volume (EDV) The volume remaining after ejection is the end-systolic volume (ESV) and the volume ejected is the stroke volume (SV) SV = EDV – ESV 16 adde byeje dam 3al heart ma sakkar 3l ekhir l valve 17  Regulation Of Stroke Volume : 1- Preload Preload is the amount of stretch on the heart prior to contraction= End diastolic pressure Within limits, greater stretch of the heart results in more forceful contraction (Frank-Starling law of the heart). The preload is directly proportional to the volume of blood in the ventricles, or EDV. end diastolic volume Two factors affect EDV: 1) duration of ventricular diastole: As ↑heart rate → duration of diastole shortens → smaller EDV → a smaller SV → CO↓ cardiac output bt2el 2) venous return, the amount of blood returning to the heart: during exercise, venous return ↑ because of increased squeezing of skeletal muscle on the veins. Consequently, SV ↑. 18  Regulation Of Stroke Volume : 2- Contractility ahamma factor hon huwe l preload Contractility is a change in the heart’s ability to do work when the preload, afterload, and HR are kept constant. Contractility is the strength of contraction at a given preload, and it is independent of muscle stretch and EDV. ma drure ktir yrteh l heart la y3ml contraction awiyye (hiye akid khassa bas msh 3atoul it's the case ex. disease m3ayyane) Although preload is the major intrinsic factor regulating SV, contractility is influenced by extrinsic factors. Substances that increase contractility = positive inotropic agents stimulation lal CA2+ la yfut 3l cytoplasm de la cellule cardiac that decrease contractility = negative inotropic agents.block calcium Positive inotropic agents generally stimulate Ca2+ influx into the cytosol of cardiac muscle fibers, strengthening the force of contraction. Such agents include glucagon, thyroxine, norepinephrine, and epinephrine. Negative inotropic agents, which impair Ca2+ inflow, include anoxia, acidosis, increased extracellular K+ levels, and calcium channel blockers. cafeine: enhances the in-flow of Ca2+ so hiye positive ionotropic agent 19  l negative ionotrop fiya t2assir 3a 7ayalla step7asab naw3a by3la2 norepineph 3l B1 recep, ATP byt7awal lal cAMP w cAMP by3ml activate la protein kinase wl kinase btftah l canal Ca2+ w b fout Ca2+ norepinephrine bicouche phospholip 20  Regulation Of Stroke Volume : 3- Afterload The pressure that must be exceeded by the ventricles before blood can be ejected through the semilunar valves is called afterload. end systolic volume Any factor that increases afterload will increase ESV and decrease stroke volume. Such factors include hypertension or narrowing of the arteries, as in arteriosclerosis. 21  Systolic and Diastolic Heart Failure Systolic heart failure is characterized by normal filling of the ventricle and a decrease in SV. It may result from a decreased bteje secondary baad l pressure w volume overload contractility (myocardial failure), from a primary increase y3ne l afterload ktir 3alyee in (aortic stenosis) ventricular pressure (Pressure Overload), or from an increase in ktir volume ex. valve tricuspide/bicusp be2e maftouh w sar ynzal blood zyede ventricular volume (Volume Overload) Myocardial Failure may be primary (e.g., dilated cardiomyopathy) or may occur secondary to chronic volume or pressure overload. aw khel2a fi myocardial failure  Systolic and Diastolic Heart Failure The most common causes for pressure overload in domestic animals are subaortic stenosis and hypertension (left-sided CHF). le2n aorte 3al left Leaking valves, an abnormal communication between the systemic and pulmonary circulations usually result in increased ventricular volume (increased preload). Decrease in contractility lowers the SV, CO, and ABP stroke volume arterial blood pressure  Diastolic Heart Failure is characterized by improper filling of ventricles. This dysfunction may be caused by : 1. An Impairied Energy ex. cAMP ma n3amallo block w be2e y3abbe Ca2+ y3ne more contraction Ventricular Relaxation, Or Myocardial Dysfunction 2. Obstruction To Ventricular Filling ex. stenose 3. Pericardial Abnormalities.  A-Concentric Hypertrophy In pressure overload states, the increase in resistance to ejected blood leads to compensatory dilation (concentric hypertrophy). ana b htde l case 3lyit pressure. la wattiya ya bwatte radius aw b3alle thickness fi 2 types of hypertrophy: whde b zid l wall thickness w whde b zid radius The decreased wall stress can be achieved by decreasing LV radius and/or by increasing LV wall thickness. With a sustained pressure overload, the ventricular muscle adapts by undergoing concentric hypertrophy, which leads to an increase in wall thickness at the = b zid wall thickness expense of a decrease in chamber size (decrease in ventricular radius), thus returning ventricular wall stress toward normal and increasing contractility. le2n mafi enough blood supply The hypertrophied ventricle is prone to ischemia, which leads to fibrosis & an collagen by3ml daght ma b khalle l alb yaamol relaxation increase in collagen content that interferes with diastolic filling, decreasing preload and SV. Therefore, in the end both systolic and diastolic dysfunction occur.  B-Eccentric Hypertrophy hon byousa3 lumen aw radius In volume overload, the increase in chamber size occurs as a result of the need to accommodate a large ventricular EDV. Dilation of the ventricle by increasing the EDV leads to a lesser increase in wall stress than in pressure overload, and it subsequently results in ventricular eccentric hypertrophy in order to normalize wall stress. Volume overload is marked by an eccentric hypertrophy with a mild increase in wall thickness in the face of a large increase in LV radius.  Neuroendocrine Compensatory : Mechanisms in Heart Failure Heart failure results in chronic activation of neuroendocrine compensatory mechanisms to restore and maintain ABP. arterial blood pressure High-pressure baroreceptors in the aortic arch and carotid sinus, mechanoreceptors in the ventricular myocardium, volume receptors in the atria and great veins, and the juxtaglomerular apparatus in the kidneys can sense alteration in ABP. A reactive neuroendocrine activation decreases parasympathetic drive (immediate and short-lived) and increases sympathetic drive (slow but long- lasting), causing vasoconstriction (increasing arterial impedance) and tachycardia. A decrease in renal blood flow leads to renin-angiotensin-aldosterone system (RAAS) activation, contributing to vasoconstriction and sodium and water retention (increases the circulating volume).  Neuroendocrine Compensatory : Mechanisms in Heart Failure The cardiomyocytes also undergo changes to adapt to ventricular dysfunction, initially by performing extra work (stable hyperfunction) but over a long period these cardiomyocytes die (exhaustion and progressive cardiosclerosis phase). The net effect of neuroendocrine activation is ✓ Vasoconstriction, ✓Sodium And Water Retention, ✓ LV Hypertrophy, ✓Coronary And Peripheral Vessel Remodeling.  Role of Catecholamines in the Progression of H Failure Dogs with CHF have increased norepinephrine (NE) secondary to NE “spillover” into plasma. Despite the increase in the plasma concentration of NE, there is depletion of NE from the atria and ventricles (secondary to β-adrenoreceptor downregulation), which blunts the response to sympathetic activation. In normal hearts, the ratio of β1 to β2 receptors is approximately 80 : 20, whereas in failing hearts, it approaches 60 : 40. The decrease in NE stores and the changes in adrenoreceptors lead to a decrease in the contractile response of the myocardial cells and in a positive chronotropic response (increased HR). Chronic adrenergic stimulation also leads to an increase in afterload, development of ventricular arrhythmias, and progression to left ventricular dysfunction.  Summary of Pathophysiology of Heart Failure Long-term overload-induced cardiac hypertrophy is accompanied by myocardial cell death and cardiac fibrosis (i.e., cardiomyopathy of overload). The ischemia resulting from hypertrophy and stretching beyond certain limits decreases contractile strength and eventually leads to loss of contractile proteins within these cells or loss of these cells. These processes result in atrophy of the affected myocardium and lead to the development of multifocal myocardial fibrosis and atrophy, which consequently interferes with diastolic function. When early interstitial fibrosis progresses to individuation of cardiac myocytes (with progression of hypertrophy), both systolic and diastolic functions are impaired. CHF is a progressive and irreversible disease with myocardial cell death and functional myocardial failure that ultimately leads to death. Pathophysiologic cycles that lead to progressive left heart failure. Cycle 1: Increased total vascular resistance increases myocardial wall stress that induces myocardial hypertrophy. Cycle 2: Water and sodium retention leads to increased preload and vascular congestion. Cycle 3: Neuroendocrine activation leads to myocardial and vascular remodeling. All cycles contribute to further myocardial dysfunction and neuroendocrine activation. Pathophysiology of heart failure