Biol 2200 Unit 5

atherosclerosis

a disease that involves the tunica intima of arteries where fibrous fatty lesions form in large or medium sized arteries, which results in wall thickness, decreased elasticity, reduced vessel radius, and ischemia to the organs

sites of atherosclerosis

abdominal aorta and iliac arteries, proximal coronary arteries, thoracic aorta, femoral and popliteal arteries, internal carotid arteries, vertebral, basilar, and middle cerebral arteries

causes of atherosclerosis

any illnesses that damage endothelial cells, including hyperlipidemia, cigarette smoke, diabetes, immune mechanisms, and turbulent blood flow

pathogenesis of atherosclerotic plaques

damage to endothelial cell lining leads to increased endothelial permeability to plasma protein and lipids; then monocytes and other leukocytes migrate into sub-endothelial layer, where monocytes will differentiate to macrophages and ingest lipids with ROS to transform into lipid filled cells called foam cells; foam cells will release growth factors that proliferate smooth muscle to form a fibrous cap over necrotic core, where it leads to progressive tissue damage and growth of plaque lesion

low density lipoproteins

a transport form of lipids in blood; they are oxidized by ROS in plaques and then eaten by macrophages

risk factors of atherosclerosis

elevated cholesterol, obesity, high blood pressure, diabetes, smoking, and sedentary lifestyle

coronary heart disease (CAD)

the narrowing or blockage of the coronary arteries; most common cause of ischemic heart disease

ischemic heart disease

disease is characterized by ischemia of the heart muscle, usually due to coronary artery disease

right coronary artery

a coronary artery that supplies mostly the right ventricle and posterior regions of the heart

left coronary artery

a coronary artery that supplies mostly the left ventricle and interventricular septum

myocardial blood flow

has two mechanisms that produces vasodilation or constriction of coronary blood vessels; highest flow happens during diastole

autonomic nervous system control of myocardial blood flow

myocardial blood flow is operated by parasympathetic nervous system via vagus nerve and sympathetic nervous system

local autoregulation of myocardial blood flow

a major control of myocardial blood flow as vasoactive mediators produce vasodilation or constriction of coronary blood vessels to fulfill oxygen demands

pathogenesis of myocardial blood flow

the disease begins with subendocardial regions of muscle being damaged due to difficulty with adequate blood flow, then there is reduced flow in subendocardial regions, which have increased compression from blood in the ventricles

collateral circulation

anastomoses exist between smaller coronary arteries, so when acute ischemia occurs, the anastomoses dilate within seconds to provide an alternative path for blood flow

pathogenesis of atherosclerosis

the disease starts with atherosclerotic plaque development in coronary arteries, then plaques bulge in the blood vessel lumens, which reduces the blood flow, which can lead to stable angina, unstable angina, acute coronary syndrome, or myocardial infarction depending on thrombus rupture

atherosclerotic plaque progression

healthy artery, lesion initiation, fatty streak, fibrous plaque, and plaque rupture

angina

pain that radiates from the sub-sternal region of the chest to the jaw and down the arms; the myocardial ischemia that occurs is temporary and no necrosis forms

stable angina

a type of angina where plaque is intact, partially obstructing coronary artery; the pain is caused by physical exertion or emotional stress; it is a temporary myocardial ischemia with no necrosis, not lasting longer than 15 minutes, and can be treated with GTN (glycerol trinitrate)

unstable angina

a type of angina where plaque is ruptured and is the least severe form of acute coronary syndrome; it is characterized by plaque instability, which leads to the development of small thromboses; chest pain happens spontaneously and lasts longer than 20 minutes; it requires immediate hospitalization due to potential of myocardial infarction and the treatments include oxygen, aspirin, nitrates, and morphine

acute coronary syndrome

a spectrum of ischemic heart diseases that are involved with rupture of plaques and thrombus formation; the symptoms include pain persisting longer than 20 minutes, pain increase, and not relieved by short acting vasodilators

myocardial infarction

the immediate result of severe coronary blockage where blood flow ceases in vessels beyond occlusion, except for small amount of collateral flow; this produces acute ischemia in the myocardium where varying degrees of ischemic injury and necrosis can occur; two different classifications of myocardial infarction called STEMI and non-STEMI

STEMI myocardial infarction

a type of MI where thrombus lodges permanently in the blood vessel and the entire thickness of the myocardium becomes ischemic; it is associated with ST segment elevation on ECG and requires immediate emergency intervention

non-STEMI myocardial infarction

a type of MI where thrombus disintegrates before complete tissue necrosis, so only subendocardium affected; the ECG shows transient ST elevation, then T wave inversion

serum cardiac biomarkers

a tool useful to diagnose myocardial infarction

manifestations of acute coronary syndrome

disease happens suddenly; there is severe and crushing pain that usually radiates to the left arm, neck, or jaw; complaints of fatigue and weakness; tachycardia, anxiety, restlessness, or feelings of doom; pale, cool, and moist skin; gastrointestinal issues, such as nausea and vomiting; can be a “silent” disease

causes of death in myocardial infarction

decreased cardiac output, fibrillation of the heart, and rupture of the heart

decreased cardiac output from myocardial Infarction

leads to cardiogenic shock and happens from reduced pumping; the continued failure of cardiac output leads to heart failure and peripheral ischemia

fibrillation of the heart from myocardial Infarction

main cause of death in STEMI is ventricular fibrillation; cardiac output is zero due to erratic electrical impulses and abnormal conduction pathways in damaged myocardium

rupture of the infarcted area from myocardial infarction

occurs several days after infarction due to muscle fibers necrosing and degenerating and the heart wall stretching thin; “systolic stretch” (dead muscle forced outward by pressure) increases to the point when finally the heart ruptures

treatments of acute coronary syndrome

oxygen therapy, anticoagulant therapy (e.g. aspirin, platelet inhibitors), nitroglycerin (GTN), beta blockers; pain relief; bed rest; ECG monitoring

bed rest

important for a myocardia infarction attack; this is due to 1) cell death is determined by degree of ischemia due to infarction and workload on the heart, so less activity means better outcomes, and 2) reduces the collateral circulation that may be assisting the damaged muscle during recovery

pain relief

important for a myocardial infarction; includes morphine; ischemic myocardium can produce severe “crushing” chest pain, hypothesized to come from lactic acid and inflammation chemical mediators; it helps with both comfort and decreasing cardiac output

reperfusion techniques

re-establishes coronary blood flow using fibrinolytic therapy, percutaneous coronary intervention (mainly stents or thrombectomy) or coronary artery bypass grafting

fibrinolytic therapy

a type of treatment therapy that breaks down clot using streptokinase

steps in electrical conduction

SA node initiates AP, which spreads to both atria and AV node, which travels to interventricular septum via AV bundle of His, which splits into left and right branches and ends at Purkinje fibers

tachycardia

fast heart rate

bradycardia

slow heart beat

sinus arrhythmia

irregular heartbeat

dysrhythmia

a range of conditions where the heart beat is being abnormal; includes occasional “missed” or rapid beats to serious disturbances that impair the pumping ability of the heart

causes of dysrhythmia

the abnormal rate of impulse generation from the SA node or other pacemaker, or the abnormal conduction of impulses through the heart’s conduction system

atrial fibrillation

most common dysrhythmia; a type of atrial conduction; completely disorganized, irregular atrial rhythm accompanied by irregular ventricular rhythm, which causes a pooling of blood in atria; treatment includes anticoagulants to prevent embolus formation

heart block

a type of atrioventricular node abnormality, which happens when conduction is excessively delayed or stopped at the AV node or bundle of His, which results in slower or lack of conduction; ultimately results in lower cardiac output

types of heart block

first degree, second degree, and third degree

ventricular fibrillation

a type of ventricular conduction abnormality, where ventricles quiver but do not contract, which leads to ineffectiveness of ejecting blood

asystole

no electrical activity in the heart or absence of a heartbeat

defibrillation

a type of treatment that helps terminate ventricular fibrillation by using an electrical shock to reset the electrical state of the heart so that it may beat to a rhythm controlled by its own natural pacemaker cells

pericarditis

acute inflammation of the pericardium, that results in pain and fever; causes include idiopathic reasons, infection, or surgery; treatment includes relief of symptoms and anti-inflammatory drugs

cardiomyopathy

a diverse group of diseases that primarily affect the myocardium; causes are idiopathic, genetic, or acquired

dilated cardiomyopathy

a condition where there is increased ventricular volume, which causes impairment of systolic function; causes include inherited, infections, chemotherapy or idiopathic; manifestations include dyspnea, orthopnea, and reduced exercise capacity; the common cause of heart failure and transplantation

hypertrophic cardiomyopathy

a condition where thickening of septum happens, which decreases left ventricular size and obstructs blood outflow; one of the most common types; often an inherited disease; mostly asymptomatic, but symptoms can include angina, dyspnea, reduced exercise capacity

valvular dysfunction

can be congenital or acquired disease that produces “murmurs”; most commonly affects aortic and mitral valves; two types of disruptions

stenosis

a type of valvular disruption that involves narrowing of valve opening that causes turbulent flow and enlargement of emptying chamber

regurgitant valve

a type of valvular disruption that permits backward flow of blood

heart failure

heart is unable to generate an adequate cardiac output, such as stroke volume and heart rate; stroke volume depends upon preload, afterload and myocardial contractility; this condition causes inadequate perfusion of tissues, or increased pulmonary capillary pressures, or both; common causes include coronary artery disease, MI, valvular disease, or cardiomyopathies

risk factors for heart failure

ischemic heart disease, hypertension, diabetes mellitus type 2, obesity, older age, lack of exercise, and smoking

preload

volume of blood in the left ventricle at the end of diastole; determined by amount of blood entering ventricle during diastole, blood left in ventricle after systole, and Frank-Starling law

Frank-Starling law

the more stretched the ventricle wall, the greater the force of the contraction

afterload

resistance to ejection of blood from the left ventricle; peripheral vascular resistance is a good indicator

inotropy

the ability of the actin and myosin of the heart muscle to interact and shorten against a load; this increases cardiac output, independent of preload and afterload

factors of inotropy

ventricular hypertrophy increases contractility, and myocardial infarction decreases contractility

systolic heart failure

myocardial contractility is impaired, which results in a decrease in ejection fraction and decreased cardiac output; more blood remains in the ventricle after contraction, thus increasing pre-load, which leads to pulmonary or peripheral edema

causes of systolic heart failure

decreased contractility (e.g., due to MI, cardiomyopathy), volume overload (e.g., valvular incompetence), and pressure overload (e.g., hypertension)

diastolic heart failure

occurs on left side; caused by decreased diastolic relaxation so that less blood enters the ventricle and leads to decreased cardiac output; causes pulmonary edema

causes of diastolic heart failure

caused by conditions that decrease expansion of the ventricle (e.g., pericardial effusion), increase wall thickness and reduce chamber size (hypertrophic cardiomyopathy), delay diastolic relaxation (myocardial ischemia/CAD; decreased energy for calcium pumps), or aging

left heart failure

can be systolic, diastolic, or both; there is decreased cardiac output to systemic circulation; when decreased cardiac output to the systemic circulation occurs, blood accumulates in the left side in the pulmonary circulation, causing increased pulmonary venous pressure, and may cause pulmonary edema

causes of left heart failure

causes include hypertension, acute MI, valve disorders, cardiomyopathy

manifestations of left heart failure

restlessness, cyanosis, fatigue, exertional dyspnea, orthopnea, tachycardia, confusion, pulmonary congestion

right heart failure

the inability of right ventricle to move deoxygenated blood from systemic circulation into the pulmonary circulation, which causes pressure to build in systematic venous circulation and results in peripheral edema and leads to congestion of the viscera

causes of right heart failure

caused by left heart failure, cor pulmonale, right heart issues (e.g. MI, cardiomyopathies, and valvular disease)

cor pulmonale

when right heart failure occurs in response to pulmonary disease not caused by left heart failure; examples include COPD, cystic fibrosis, ARDS, which increase pulmonary pressure

compensatory mechanisms of heart failure

sympathetic nervous system activation, RAAS activation, hypertrophy

sympathetic nervous system activation of heart failure

increases blood pressure and cardiac output; however this causes increase in heart rate, contractility, and blood pressure, and puts more strain on the already weakened heart

Renin-Angiotensin Aldosterone System (RAAS) activation of heart failure

leads to release of ADH; leads to vasoconstriction that increases afterload and leads to increased blood volume that increase pre-load; both of which put more strain on the heart

hypertrophy of heart failure

a disproportionate thickening of the ventricle walls, which increases ischemia, or thinning of the ventricular walls, which leads to dilation and impairment of contraction

symptoms of heart failure

fatigue and tires easily, decreased urine output, dyspnea, orthopnea, edema, weight gain

orthopnea

difficulty breathing when lying flat

treatment for heart failure

concentrates on decreasing preload and afterload; salt restriction, diuretics, and weight management, digitalis, beta blockers, and oxygen therapy

shock

acute failure of the circulatory system to supply the body with an adequate blood supply, resulting in cellular hypoxia; ultimately proceeds to organ failure and death

manifestations of shock

symptoms vary depending on situation; can include report being sick, weak, cold, hot, dizzy, confused, afraid, thirsty, short of breath; only consistent sign is hypotension where mean arterial pressure is below 60 mm Hg

cellular effects of shock

cell switches to anaerobic respiration when lacking oxygen, which produces far less ATP and leads to the cell’s sodium/potassium pump to operate poorly; ion concentrations of Na, K, and Ca are not maintained, which interferes with the nervous and muscular systems

positive feedback loops of shock

sodium concentrations, lysosomal enzymes, and acidic environment

sodium concentration positive feedback loop

excessive sodium enters the cell, which leads to excessive water coming; interstitial fluids then pull water out of the vascular system, which results in a drop in blood pressure; decreased volume in the vascular system intensifies the decrease in perfusion of tissues

lysosomal enzymes positive feedback loop

disrupted cell membranes due to low ATP and cell swelling release lysosomal enzymes that damage tissues; the damaged tissues actives an inflammatory response, resulting in further damage to tissues and impairment of cellular metabolism

acidic environment positive feedback loop

acidic conditions affect hemoglobin, which decreases its affinity to bind oxygen, which results in a decrease in the oxygen carrying capacity of the blood, which further increases the tissue hypoxia

cardiogenic shock

a type of shock where there is enough blood volume, but decreased cardiac output; happens due to decreased contractility, increased preload, and/or increased afterload; the decrease in blood pressure causes compensation, such as an increase in epinephrine release and activation of RAAS system and an increase in oxygen/nutrient demand of the heart; this leads to further strain on the heart, which results in it becoming incapable of pumping; often follows a myocadiac infarction; often unresponsive to treatment

hypovolemic shock

a type of shock where blood volume is not enough; causes include loss of blood (e.g. hemorrhage), plasma (e.g. burns), or interstitial fluid (e.g. diuretics, diarrhea); some compensatory mechanisms include HR and vasoconstriction increase, interstitial fluid moves into blood, liver and spleen add to blood volume, and RAAS and ADH activated to help bring blood volume higher; treatment includes rapid fluid replacement

distributive shock

type of shock that occurs from massive vasodilation; blood volume has not changed but the amount of space containing the blood has increased, which causes a decrease in blood pressure and a decrease in nutrient exchange across capillary membranes to cells; three types called neurogenic, anaphylactic, and septic

neurogenic shock

a type of distributive shock where it results from overstimulation of the parasympathetic nervous system and under-stimulation of the sympathetic nervous system; causes include trauma to spinal cord or medulla

anaphylactic shock

a type of distributive shock that occurs from anaphylaxis; the release of histamine by mast cells results in vasodilation and vascular permeability to the point of tissue edema and peripheral pooling; can result in laryngospasm, bronchospasm, and diarrhea; onset is usually very sudden and progression to death can
occur within minutes; treatment includes intramuscular administration of epinephrine

septic shock

most common type of vasodilatory shock; results from severe infection with a microbe, often due to the toxins or microbe itself; death occurs often in intensive care units; signs include wide spread vasodilation

obstructive shock

shock that results from mechanical obstruction of the blood flow through the central circulation (great veins, heart or lungs); causes include pulmonary embolism, cardiac tamponade, and pneumothorax

treatment of shock

must remove underlying cause, IV fluid to expand blood volume, vasopressors, and supplemental oxygen

manifestations of atherosclerosis

coronary artery disease, peripheral artery disease, thrombus formation, possibility of aneurysm or stroke, heart attack

peripheral artery disease (PAD)

obstruction of peripheral arteries can cause significant pain and disability; common in diabetics

treatments of atherosclerosis

prevention of plaque progression, such as exercise, quit smoking, control of hypertension, reducing LDL with diet or drugs; surgical interventions, medications

hypertension

the condition of consistent elevation of systemic arterial blood pressure; higher risk for myocardial infarction, stroke, and kidney disease; two types called primary and secondary

primary hypertension

a type of hypertension produced by a combination of genetics and
the environment, and other factors such as family history, age, race, sodium intake, insulin resistance, obesity, and cigarette smoking; determined by blood pressure measured at different times, and other tests, such as complete blood count, urinalysis, blood chemistry

causes of hypertension

the increased blood pressure is due to an increase in circulating blood volume and an increase in peripheral resistance; this can happen by some mechanisms, such as sympathetic nervous system (increases heart rate and vasoconstriction), overactivity of renin-angiotensin-aldosterone system (increases vasoconstriction and blood volume and pressure by retaining sodium and water in kidneys), and chronic inflammation that results in smooth muscle contraction

manifestations of hypertension

early stages have no signs; majority of signs become evident when damage to other organ systems occur