N715 Exam 3 Part 1 PDF

Final Exam -- cumulative December 4-9 **FINAL EXAM REVIEW ON DEC 3 4:00-5:00 Week 10 Cardiovascular overview afterload is cardiac output- the force against which the heart has to push Contractility is the pump Preload is what we return to the heat, the venous system- what goes on...

Final Exam -- cumulative December 4-9 **FINAL EXAM REVIEW ON DEC 3 4:00-5:00 Week 10 Cardiovascular overview afterload is cardiac output- the force against which the heart has to push Contractility is the pump Preload is what we return to the heat, the venous system- what goes on in it directly affects what is delivered to the right atrium for delivery to the lungs for oxygenation View of the cardiovascular system Major blood vessels and minor blood vessels Veins have valves the return the blood to the heart or provide the preload The arterial system provides the afterload Terminates in the capillary beds (e.g. bowmans capsule in kidney, capillaries in alveoli in lungs) Results ultimately in perfusion to tissue beds  The pump is the heart Flow: superior vena cava, right atrium, right ventricle, pulmonary artery, pulmonary vascular bed (exchange of co2 and oxygen), newly oxygenated blood returned to heart via pulmonary veins to left atrium (low flow system), left ventricle, aortic valve into the aorta then into systemic circulation Along the aortic root we see the origination of the coronary arteries The left main coronary artery supplies the circumflex artery that comes around the back of the heart and supplies the lateral and posterior aspect of the heart the left anterior descending artery supplies the majority of the left ventricle which is the most important chamber of the heart and the septum where the bundle of his is that extends into the Purkinje fibers The right coronary artery supplies the nodal tissues in the atrial node and the AV node (nodal tissue needs to be perfused, if they don’t have oxygen to generate ATP they wont generate conduction of electrical impulses)- manifests as bradycardia, heart blocks, asystole PR – atrial conduction cycle P wave- atrial depolarization Atria repolarize during the QRS interval; also during this interval we see atrial kicks- extra kick of right atrium where it supplies approximately 20 percent of blood volume to the right ventricle QRS interval is ventricular depolarization QT interval- represents the ventricular conduction cycle A prolonged QT interval gets caught up into the next conduction cycle- the P wave, and throws everything off (manifestations include torssades, ventricular tachycardia, ventricular fibrillation- can lead to death) The conduction system moves from the sinoatrial node through the internodal pathway between the two nodes (SA and AV) – pathology can be seen here- reentry phenomenon and differential atrial dysrhtymias SA node then AV node then bundle of his then left and right bundle branches then fascicles and Purkinje fibers Electrical conduction of impulses to the heart may or may not result in cardiac contractility Heart cells have the characteristic of automaticity – each cardiac cell has the ability to generate its own action potential Heart cells work together in unison- cells do not fire individually We all have abnormal or ectopic heart beats- happens when one or more of the heart cells is somehow stressed, cells generate their own automatic action potential, which sometimes results in cardiac contractility- we see not only conduction but mechanical contraction of the heart that is generated by these abnormal beats that are not in sync with the normal PQRS sequence Sliding theory- movement of actin, myosin, and troponin with the intercalated discs Intercalated discs are what helps the mechanical movements of the cardiac tissue to work in a unison Perfusion Pulmonary system is low flow When blood leaves the left ventricle, there is normal blood pressure (120/80) Pressure is low coming from the venous system Very Low pressures in the right atrium, reflects the central venous pressure (0-4), affected by respiration Entry into Right ventricle- increasing pressure due to atrial kick and contraction of right atria and ventricle, right ventricular pressure should reflect pulmonary artery pressure Pulmonary hypertension is a pulmonary artery pressure that is over a mean of 35 Left atrial pressure should be the same as the pulmonary capillary occlusion or wedge pressure If pressure is too high, we see end organ failure End organs: brain, heart, kidney, eyes, peripheral vascular system Frank-starling law: the heart will pump most effectively if we have a good fill of the ventricles but not so overfilled with so much pressure that the heart cant work against it Cardiac output= heart rate x stroke volume Affected by autonomic innervation- presence of different catecholamines such as norepinephrine, epinephrine, different hormones  *** emphasized Condition of heart tissue affects stroke volume (e.g. ischemic tissue) EDV= end diastolic volume Preload is affected if we have too much volume The neurohumoral responses include the natriuretic system and the RAAS system  ○ Naturetic pepties- proteins, produced to cause vasodilation and decrease sympathetic tone, so that we are not retaining sodium and eliminating fluid if the pressure in the vascular system is too high ○ BNP- brain naturetic peptide ○ RAAS- works to increase blood pressure, if a patient is hypotensive, we want to pull more pressure and volume into the vascular space- tightens up sympathetic tone and increases retention of sodium (and fluid) through the release of aldosterone –angiotensin is the most potent vasoconstrictor in the body and leads to production of aldosterone Cardiopulmonary circulation at birth Heart is fully developed at 35 weeks Formation of septum Formation of foramen ovale Can see how easily congenital anomalies can come about Looping needs to occur in this pattern  Septation ○ Partitioning of the AV canal, primordial atrium, ventricle, and outflow tracts begins around the middle of the 4th week and is completed by the 8th week ○ Septation occurs concurrently ○ 4th week: Endocardial cushions form on the dorsal and ventral walls of the AV canal These cushions approach each other and fuse, dividing the AV canal into left and right AV canals Partitioning of the aorta ○ Primordial atria is divided into left and right by the formation and subsequent modification and fusion of 2 septa – septum primum and septum secundum Partitioning of the ventricles ○ Division of the left and right ventricles occurs by growth of the muscular intraventricular septum from the floor of the ventricle ○ Completed by fusion of endocardial cushions with bulbar ridges by end of 7th week Partitioning of aorta and pulmonary trunk ○ During the 5th week, proliferation of mesenchymal cells in the walls of the bulbus cordis results in formation of bulbar ridges. ○ Similar ridges form in the truncus arteriosis ○ Concurrently, the bulbar and truncal ridges spiral 180 degrees which leads to creates spiral aorticopulmonary septum when ridges fuse ○ Septum creates two arterial chambers: aorta & pulmonary trunk Development of cardiac valves ○ Semilunar valves (aortic and pulmonary valves) develop from 3 swellings of the subendocardial tissue around the orifices of the aorta and pulmonary trunk (neural crest cells are also involved) These swellings hollow out and reshape to form three thin-walled cusps ○ Atrioventricular valves (tricuspid and mitral valves) develop similarly from localized proliferations of tissue around the AV canals. Conducting of the heart system ○ The sinoatrial node develops in the 5th week Located in the right atrium near the entrance of the SVC ○ AV node located just superior to the endocardial cushions. ○ The atrium and ventricle become electrically isolated from each other by fibrous tissue, with only the AV node and bundle conducting impulses. ○ Fibers arising from the AV bundle pass from atrium to ventricle and split into right and left bundle branches, which are distributed through ventricles Fetal circulation  ○ Fetal circulation reflects the fact that oxygenation does not occur in the lungs Only 5-10% of fetal blood passes through lungs ○ The pulmonary system is bypassed: Patent foramen ovale Patent ductus arteriosus ○ Pulmonary vascular resistance is high in utero Transitional circulation ○ Once umbilical cord is clamped, Systemic Vascular Resistance rises and exposure to oxygen causes Peripheral Vascular Resistance to fall ○ Ductus venosus closes from lack of blood flow from placenta ○ Functional closure of the PFO from increased left sided pressures compared to right ○ Functional closure of the PDA (usually in first 24 hrs) due to increased oxygen tension and falling levels of prostaglandins (produced by the placenta), which function in utero to maintain patency of DA ○ With clamping of cord and exposure to oxygen, pulmonary vascular resistance falls, lungs inflate, left sided pressure of heart increases which all leads to closure of PFO and eventually PDA Heart wall ○ Pericardium: Double-walled membranous sac Parietal: surface layer Visceral: inner layer (epicardium) Pericardial cavity is space between 2 layers, contains pericardial fluid (20mL) ○ Epicardium: outer smooth layer ○ Myocardium: Thickest layer of cardiac muscle ○ Endocardium: Innermost layer ○ Coronary vessels lie between myocardium & epicardium Coronary circulation ○ Supplies oxygen and other nutrients to the myocardium ○ Right & Left coronary arteries (openings in semilunar valves at entrance to the aorta) ○ Coronary veins- enter RA via coronary sinus ○ Collateral arteries – connections; protect from ischemia Cardiac cycle ○ Cardiac cycle: ○ 1 contraction & 1 relaxation ○ Make up 1 heart beat ○ Diastole: Relaxation when Ventricles fill ○ Systole: Contraction when Blood leaves ventricles Conduction system ○ Propagation of cardiac action potentials ○ Depolarization: Activation  ○ Inside of the cell becomes less negatively charged. ○ Repolarization: Deactivation ○ ○ Refractory period Heart muscles cannot contract. Ensures that diastole (relaxation) will occur. Completes the cardiac cycle. Myocardial Infarction Ischemia to the myocardium results in: ○ Electrolyte imbalance ○ Catecholamine release ○ Angiotensin II release ○ Severe inflammatory response ○ Heart failure ○ 8-10 seconds for myocytes to convert from aerobic to anaerobic respiration-As hydrogen ions and lactic acid accumulate, the heart quickly experiences structural and functional changes that lead to heart failure ○ Myocytes can tolerate 20 minutes of ischemia before irreversible damage and apoptosis occur ○ Oxygen deprivation results in electrolyte imbalances, catecholamine release, angiotensin 2 release and severe inflammation ○ Cardiac cells lose potassium, calcium, and magnesium which are all essential to the cells contractility and this can lead to dysrhythmias ○ Angiotensin 2 is a vasoconstrictor that causes coronary spasm and fluid retention, it also contributes to cardiac remodeling ○ Necrotic tissue is replaced by scar tissue and this new tissue will not have the same contractility as cardiac tissue Reperfusion injury ○ As coronary blood flow is restored, reactive oxygen species/ free radicals are released and calcium is influxed back into cells, this causes increased mitochondrial permeability and cell death ○ Myocardial stunning- temporary loss of contractile function – reversible once ROS and calcium influx subside ○ Hibernating myocardium- some areas of heart stop working temporarily ○ Release of toxic oxygen free radicals ○ Calcium influx ○ Increased mitochondrial permeability ○ Disrupted coronary circulation Functional changes of the heart ○ Myocardial remodeling: myocyte hypertrophy following injury ○ Decreased contractility ○ Altered LV compliance  ○ Decreased stroke volume & ejection fraction ○ Increased left ventricular end-diastolic pressures ○ Alterations to SA node Increased risk for dysrhythmias ○ Angiotensin 2, aldosterone, catecholamines, and inflammatory cytokines all contribute to cellular hypertrophy of the myocardium Clinical manifestations ○ Sudden, severe chest pain (more severe & prolonged pain than that w/ angina pectoris) Described as “heavy” or “crushing” ○ Radiation to neck, jaw, back, shoulder, or left arm ○ Infarction often simulates a sensation of unrelenting indigestion ○ Shortness of Breath (SOB) / Dyspnea ○ Vasovagal reflex from area of the infarcted myocardium Nausea/Vomiting (N/V) dt reflex stimulation of vomiting centers by pain fibers Lightheadedness, Dizziness, or Fainting / Syncope Diaphoresis May affect GI tract (abdominal pain or discomfort) ○ SNS reflexively activated to compensate for MI → inc. HR & BP then decompensation can be seen w/ dec. HR & BP ○ Abnormal, extra heart sounds reflect LV dysfunction or mitral regurgitation murmur ○ Pulmonary findings: Rales or Wheezing If pt develops HF: JVD, dullness on percussion, inspiratory crackles at lung bases Pericarditis: pleural rub ○ Peripheral vasoconstriction → cool, clammy skin may see cyanosis or pallor (w/ HF) complications ○ # and severity of post-infarction complications depend on: location & extent of necrosis, the individual’s physiological condition before the infarction, and the availability of swift therapeutic intervention ○ Sudden death can occur in individuals w/ MI even if infarction is absent or minimal ○ Risk for sudden death rt interaction among 3 factors: ischemia, LV dysfunction, and electrical instability ○ Dysrhythmia (A-Fib, ventricular arrhythmias, palpitations, etc.) ○ Left ventricular failure → Cardiogenic shock ○ Pericarditis ○ Dressler post-infarction syndrome ○ Organic brain syndrome dt impaired brain blood flow ○ Rupture of chordae tendineae  ○ Aneurysm and rupture of wall or septae of infarcted ventricle dt high chamber pressures & volume ○ Systemic arterial thromboembolism ○ Pulmonary thromboembolism usually from DVT of the legs NOTES W/ MYOCARDIAL INFARCTION Transmural STEMI v Subendocardial NSTEMI Differences in clinical manifestations from men v women and dependent on conditions ○ For example, diabetic or transplant patient may not have pain -- neuropathy & no pain fibers ○ Women’s top complaint is fatigue followed by dyspnea Ischemia affecting different areas of the heart & how they’d present in the case of MI Heart Failure Patho Begins with insulting injury to cardiac tissue, which is most commonly myocardial infarction, other injuries include valve damage/malfunction-aortic stenosis, or abnormally high heart rate- a-fib, or from infection like myocarditis EF is measured in left sided heart failure to determine severity of symptoms Insulting injury - MI, valve damage, high HR Ejection fraction = stroke volume/end diastolic volume ○ % of blood pumped out of the heart with each contraction Heart failure with reduced ejection fraction ○ Ejection fraction ≤40% ○ Ventricular remodeling ○ Contractile dysfunction of sarcomeres ○ Stroke Volume ↓ ○ Left Ventricular diastolic volume ↑ ○ Aka systolic heart failure ○ At time of initial injury, some cardiomyocytes are lost due to necrosis, apoptosis or autophagy and dying myocytes release intracellular proteins in circulation and trigger and inflammatory response ○ Inflammation leads to proliferation of cardiac fibroblasts that secrete extracellular matrix proteins such as collagen that take the place of the dead myocytes ○ Overtime preload continues to rise and the fibrotic tissue continues to develop in response to wall stress, which stimulates hypertrophy, wall thinning, and left ventricle dilation in a vicious cycle of ineffective ventricular diastole Neurohormonal remodeling  ○ Sympathetic nervous system activation -> catecholamines Vasoconstriction ○ Hypothalamus -> increased ADH (retention of water and sodium which increases plasma volume ) ○ Decreased renal perfusion -> RAAS ○ Stretching of tissue -> natriuretic peptides (BNP) Diuresis/vasodilation ○ Thick myocardium, relative ischemia Electrophysiological remodeling ○ Increased risk for vTach or vFib ○ Mechanisms: Na/Ca exchanger Myocardial fibrosis Leakage of Ca from sarcoplasmic reticulum ○ LATE DEPOLARIZATION -> INCREASED VENTRICULAR ACTIVITY Heart failure with preserved ejection fraction ○ Have symptoms of heart failure but maintain EF above 50% ○ Inadequate relaxation of LV making it smaller than normal during diastole and increasing wall tension ○ More cases with women, obesity, hypertension ○ Decreased compliance of LV -> wall tension during diastole -> backfilling into L atrium and pulmonary vessels ○ Hypertrophy of LV ○ Inflammation Right sided heart failure ○ Often a result of left sided heart failure when there is backflow or tricuspid regurgitation into pulmonary circulation ○ Increased preload in R ventricle ○ Peripheral edema Hepatosplenomegaly ○ Chronic hypoxic pulmonary disease ○ Inability of right ventricle to provide adequate blood flow into pulmonary circulation ○ Resistance to emptying of the right ventricle develops which causes an increased afterload ○ If right sided heart failure occurs in absence of left sided, likely due to diffuse hypoxic pulmonary diseases such as COPD or cystic fibrosis ○ Chronic hypoxia and increased pulmonary vascular resistance contribute to decreased contractility of the right ventricle and increased preload ○ Rise in systemic circulation, causes classic signs of full body edema and hepatosplenomegaly Clinical manifestations Kawasaki Disease Patho Acute febrile systemic vasculitis targeting medium sized vessels, closely linked to myocarditis and coronary artery aneurysms Unclear etiology. Theories: ○ Genetic predisposition ○ Viral exposure (Epstein-Barr, Coronavirus, Retrovirus) ○ Developing immune system ○ Abnormal immune response to common antigens Diagnostic criteria Fever of at least five days > Four of the following: ○ Bilateral conjunctival injection without exudate (redness of the eyes) ○ Oral changes (cracked lips, strawberry tongue, erythema)- strawberry tongue ○ Unilateral cervical lymphadenopathy >1.5 cm ○ Extremity changes(periungual desquamation,palms/soles of feet turn red) ○ Polymorphous rash without vesicles/crusting Nonspecific findings ○ Myocarditis, pericarditis ○ Diarrhea ○ Arthralgias ○ Proteinuria, WBCs in urine sediment- inflammation causes kidneys to leak ○ Decreased RBC/hemoglobin, thrombocytosis- elevated platelet count which increases risk for clot formation ○ Elevated ESR, CRP Clinical manifestations Complications ○ Possibility that there will be aneurysms forming in the proximal aspect of the coronary arteries ○ Myocarditis Stage 1 (up to 12 days)- begins with the fever ○ Inflammation of capillaries, arterioles/venules, myocardium  Stage 2 (Days 13-25) ○ Acute necrotizing vasculitis- breakdown of cells within the lining of the arteries ○ If arteries are weak or there is the presence of neutrophil elastase then we see weakening of the vascular structures Aneurysm formation Stage 3 (Days 26-40) ○ Granulation, loss of elasticity- stiffness, increased viscosity (thickening) of coronary arteries ○ *Risk for thrombosis Stage 4 (> Day 41) ○ Activation of myofibroblasts, intimal thickening, scar formation ○ Left ventricular dysfunction Inflammatory response ○ Vasculopathy (3 processes): Necrotizing arteritis- loss of elasticity and cellular death in the tunica media of the arterial structure (aneurysm formation and possible rupture) Subacute/chronic vasculitis- damage to the vessel leads to scarring and vascular dysfunction Luminal myofibroblastic proliferation (LMP)- a thickening of the intimal lining , scarring, results in dysfunction ○ Innate response: Invasion of neutrophils Neutrophil elastase Activation of dendritic cells, macrophages TNF-alpha, IL-1 ○ Adaptive response: CD8 cytotoxic killing Increased production of Th-17 cells Invasion of endothelium-LMPs Decreased function and synthesis of Treg Tetralogy of Fallot Patho Parts of the heart do not develop properly which causes insufficient blood flow to the lungs Four defects: ○ right ventricular hypertrophy ○ aorta displacement, ○ pulmonary stenosis ○ ventricular septal defect hole in septal wall, allows unoxygenated blood and oxygenated blood to mix together  ○ hole in septal wall which separates the right and left ventricles stenosed pulmonic valve results in decreased pulmonary blood flow ○ Pulmonic valve is stenosed which means blood is being pumped through a narrow artery which causes the right ventricle to have to work harder to get the blood to the lungs (decreased pulmonary blood flow) enlarged right ventricle (hypertrophy) increases risk of heart failure aortic valve displacement: hypertrophy pushes the aorta over the septal wall defect opening causing mixed oxygenated and de-oxygenated blood to distribute throughout the body resulting in the "right to left shunt" ○ Aortic valve is enlarged and moves the aorta over the septal wall that has the defect opening, this causes the mixed blood to get sucked up into the aorta and sent throughout the body (right to left shunt) on a cellular level: mitochondrial dysfunction, decrease in activity of specific enzymes in the mitochondrial respiratory chain mitochondria = powerhouses of the cell (energy production) ---> decrease in cellular energy is the basis of this condition cyanosis leads to tissue hypoxia and cell death overcompensation in red blood cell production as a result defects ○ Pulmonary stenosis Narrowing of valve Harder for deoxygenated blood to get to the pulmonary circulation Causes obstruction of pulmonary blood flow, which leads to right ventricle hypertrophy and increased pressure on the right ventricle- increased pressure causes right to left shunting which means deoxygenated blood goes into systemic circulation ○ Right ventricular hypertrophy The Right ventricle is working harder to push blood past the stenosis into the pulmonary circulation Boot shaped presentation on x-ray due to upturned apex of the heart ○ Ventricular septal defect Deoxygenated blood goes into left ventricle which goes into systemic circulation causing hypoxemia Large defect that allows shunting of blood between ventricles In TOF RVOT stenosis causes pressure in the right ventricle to increase which means that deoxygenated blood will shunt over to the left ventricle and mix with oxygenated blood and be sent into systemic circulation ○ Overriding aorta Displacement of the Aorta over the VSD Allows for Aorta to receive blood from both right and left ventricle Clinical manifestations Cyanosis Fusiness  Tire quickly Clubbing Murmur Avg pulse ox is 79% when standing and 84% when squatting Tet spells- episodic hypercyanotic spells ○ Transient near occlusion of right ventricular outflow tract ○ Results in profound cyanosis ○ Arise when infant becomes agitated or upset or during feeding ○ Occur in setting of pain, fever, anemia, after bm or feeding, hypovolemia ○ After vigorous exercise ○ Occur due to increased oxygen demand- causes HR to increase and then more deoxygenated blood mixes into the right ventricle and goes out into systemic circulation ○ Prompt intervention essential for acute episode ○ Infants and children with cyanotic episodes should be referred for surgical intervention to prevent potentially life threatening occurrences ○ Characterized by hyperpnea (rapid and deep respirations), irritability, inconsolability, and progressively severe cyanosis ○ Older children will squat down to relieve these spells ○ Though some episodes may resolve spontaneously, prolonged spells can progress to loss of consciousness and cardiac arrest WEEK 10 Cardiovascular 1. Identify the key components of cardiac output and overall tissue perfusion: Preload, afterload, and contractility Cardiac Preload Definition Preload is the volume and pressure inside the ventricle at the end of diastole, influenced by: end-systolic volume: Blood left in the ventricle post-systole, dependent on ventricular contraction strength and resistance to emptying. Venous return: Blood volume and flow through the venous system to the ventricle during diastole. Measurement Estimated using  central venous pressure (CVP) for the right heart and pulmonary artery wedge pressure for the left heart. Normal values: CVP: 1 to 5 mm Hg Pulmonary artery wedge pressure: 4 to 12 mm Hg Clinical Implications Increased preload can cause heart failure resulting in: Decline in stroke volume. Increased ventricular end-diastolic pressure (VEDP), leading to: Pulmonary edema (fluid accumulation in lung tissues). Peripheral edema (fluid accumulation in peripheral tissues). The Frank-Starling Law Relates the resting sarcomere length (end-diastolic volume) to tension generation (left ventricular pressure). The heart's contraction strength increases with sarcomere stretching up to an optimal point. Mechanisms Length-Tension Relationship Preload (filling pressure) is an index of ventricular volume. Maintains equal output from right and left ventricles despite varying stroke outputs during respiration. Example: Lying down increases venous return, stretching the right ventricle and increasing its contraction force, which raises pulmonary and subsequently left ventricular filling pressure and volume. Heart Failure Failing hearts, where fibers are over-stretched, exhibit a progressive decline in contraction force despite increased filling. The failing heart's contractility diminishes due to excessive stretching, disrupting actin-myosin cross-bridges, resulting in decreased force of contraction. Practical Analogy Compared to a rubber band: Within its limit, the more it stretches, the farther it flies. Beyond the limit, it breaks; similarly, overstretched myocardial fibers lose contraction strength without actually breaking like a rubber band does Laplace Law Formula and Variables Laplace equation: ( T = \frac{p \times r}{2 \times \mu} ) ( T ) (wall tension) is directly proportional to intraventricular pressure (( p )) and internal radius (( r )), and inversely proportional to wall thickness (( \mu )). Applications Helps in understanding how ventricular wall stress varies with changes in pressure, ventricular size, and wall thickness. Clinical Relevance 2. Supports the comprehension of heart mechanics in conditions like: a. Ventricular hypertrophy: Thickened walls decrease tension for a given pressure. b. Dilated cardiomyopathy: Increased radius increases wall tension, taxing the heart's pumping ability further Afterload Ventricular afterload refers to the load against which the heart muscle must contract to eject blood during each heartbeat. The primary index of afterload is the aortic systolic pressure For blood to be pumped out of the ventricle, the pressure within the ventricle must exceed the pressure in the aorta. Key Points: Resistance to Ejection: Afterload represents the resistance that the ventricle needs to overcome. Aortic Systolic Pressure: This serves as an index of afterload. Impact on Ventricular Function: Higher afterload means the heart must work harder to eject blood. 2. Factors Influencing Afterload The two primary factors affecting afterload are aortic pressure and systemic vascular resistance. Aortic Pressure Aortic pressure must be surpassed by ventricular pressure for blood to be ejected during systole. Variations in aortic pressure impact how quickly and efficiently the heart can contract. Low Aortic Pressure: Enables more rapid and efficient cardiac contraction. High Aortic Pressure: Slowdowns contraction, increasing the cardiac workload. Systemic Vascular Resistance (SVR) Systemic Vascular Resistance refers to the resistance blood faces from the systemic blood vessels. It is a critical determinant of afterload and is influenced by factors such as blood vessel diameter and blood viscosity. Increased SVR: Leads to increased afterload, requiring the heart to work harder to eject blood. Chronic high SVR, as observed in hypertension, can result in ventricular hypertrophy. SVR Calculation: SVR is calculated by dividing mean arterial pressure by cardiac output. The normal range for SVR is approximately 700 dyne/s/cm−5. 3. Clinical Implications of Afterload Hypertension and Afterload Individuals with hypertension often exhibit increased SVR, leading to elevated afterload and higher cardiac workload. This chronic condition can result in myocardial hypertrophy and other cardiac complications. Aortic Valvular Disease Changes in afterload can also be due to aortic valvular disease, where the morphology or functionality of the aortic valve affects the resistance to ventricular ejection. Myocardial Contractility 1. Ventricular Myocardial Stretch (Preload)  Definition: The stretch of the ventricular myocardium caused by changes in the volume of blood filling the heart (end-diastolic volume or preload). Mechanism: Increased venous return to the heart increases ventricular stretch, enhancing preload. Impact Positive: Up to a certain point, an increase in preload boosts stroke volume and cardiac output. Negative: Excessive preload can decrease stroke volume. 2. Inotropic Stimuli Definition: Substances that alter the force of ventricular contraction. Types and Sources Positive Inotropic Agents: Hormones and neurotransmitters like epinephrine and norepinephrine from the sympathetic nervous system. Negative Inotropic Agents: Acetylcholine from the vagus nerve. Medications: Various drugs can also act as inotropic agents. Pathological Conditions: In sepsis, cytokines such as TNF-α and interleukin-1β can impair myocardial contractility. Impact: Inotropic agents significantly influence cardiac function. Positive inotropes enhance contractility, whereas negative inotropes diminish it. 3. Myocardial Oxygen Supply Influence Factors: O2 and CO2 levels in the coronary blood. Impact Severe Hypoxemia: Significantly reduced arterial O2 saturation (