PATHO - Term Test II (Cardiovascular System) Flashcards

Question

Function of ventricles

Answer 1

* contract to push blood through pulmonary and systemic vessels * high pressure and thicker walls

Answer 2

~92mmHg (that's why LV is 3x thicker than RV)

Answer 3

MAP = DBP + 1/3(SBP - DBP) ex. someone with 120/80 BP MAP = 80 + 1/3(120-80) = 93 Normal range: 70-110 mmHg

Answer 4

crescent/triangle - enables a bellow-like action that efficiently ejects large volume through pulmonary SL valve into low pressure pulmonary system

Answer 5

Bullet-shaped - allows generation of enough pressure to eject blood through relatively large aortic SL valve into high pressure systemic circulation

Answer 6

to separate R and L sides and prevent blood from crossing between the two circulatory systems

Answer 7

* opening between R and L atria (because fetus does not depend on lungs for oxygenation) * functionally closes at time of birth as higher pressure in LA pushes septum primum flap closed which closes the opening * in 75-80% of infants, these septa are permanently fused within first year of life

Answer 8

4 rings of dense fibrous tissue - provides a firm anchoring for attachments of atrial and ventricular muscles, and valvular tissue they form a central fibrous supporting structure (**annuli fibrosi cordis**)

Answer 9

atrioventricular (AV)

Answer 10

**Opens:** when intraventricular pressure exceeds aortic and pulmonary pressures (allows blood to flow out of ventricles and into the pulmonary and systemic circulations) **Close:** when intraventricular pressure falls (after ventricular contraction and ejection) and pressure in vessels is greater than pressure in ventricles (to prevent backflow)

Answer 11

* composed of tissue flaps (leaflets/cusps) attached at the upper margin to a ring in the heart's fibrous skeleton & by **chordae tendinae** at lower end to the papillary muscles (extensions of myocardium) * papillary muscles hold cusps together and downward at the onset of ventricular contractio nto prevent backward expulsion or **prolapse** into atria * **tricuspid valve:** in R heart, 3 cusps * **mitral/bicuspid valve:** in L heart, 2 cusps * ALL structures form the **mitral and tricuspid complex** (atria, fibrous rings, valvular tissue, chordae tendinae, papillary muscles, ventricular walls) * damage to any one of these 6 components may alter function and contribute to HF

Answer 12

1) three cup-shaped

Answer 13

superior and inferior VC

Answer 14

pulmonary artery (which divides into right and left branches to transport unoxygenated blood from right heart to lungs) branches further into pulmonary capillary beds to gas exchange units

Answer 15

Four pulmonary veins - two from the right lung and two from the left

Answer 16

Cardiac cycle

Answer 17

**Diastole:** period of relaxation; when blood fills the ventricles **Systole:** period of ventricular contraction; blood is propeled out of ventricles and into pulmonary and systemic circulations * note: contraction of the left ventricle occurs slightl earlier than that of RV

Answer 18

**1) Atrial systole** - atria contract, pushing blood through AV valves into ventricles; SL valves are closed **2) Beginning of ventricular systole** - ventricles contract, increasing pressure within ventricles; AV valves close, causing the first heart sound **3) Period of rising pressure** - SL valves open when pressure in ventricle exceeds that in the arteries; blood pushed into aorta an dpulmonary arteries **4) Beginning of ventricular diastole** - Pressure in relaxing ventricles drops below that in the arteries; SL valves close causing second heart sound **5) Period of falling pressure** - blood flows from veins into relaxed atria; AV valves open when pressure in ventricles falls below that of the atria

Answer 19

**Originate at:** upper edge of aortic semilunar valve cusps **Receive blood:** through **coronary ostia** (openings in aorta)

Answer 20

right atrium coronary sinus

Answer 21

RCA and LCA

Answer 22

Coronary arteries are smaller in women than in men because women's hearts weigh proportionally less than men's hearts

Answer 23

**Origin:** arises from single ostium behind left cusp of aortic SL valve **Structure:** ranges from few mm - cms long * passes between L arterial appendage and pulmonary artery * divides into two branches: LAD and circumflex artery * other branches are distributed diagonally across the free wall of the LV

Answer 24

**Structure:** arises from LCA; travels down anterior surface of interventricular septum toward apex of heart **Function:** delivers blood to portions of L and R ventricles and much of interventricular setpum

Answer 25

**Structure:** travels in a groove (coronary sulcus) that separates LA from LV and extends to left border of heart; often branches to posterior surfaces of LA and LV **Function:** supplies blood to LA and lateral wall of LV

Answer 26

**Originates:** from ostium behind R aortic cusp **Structure/Function:** travels behind pulmonary artery, extends around R heart to heart's posterior surface where it branches to atrium and ventricle; three major branches: * conus (supplies blood to upper right ventricle) * right marginal branch (supplies RV to the apex) * posterior descending branch (lies in posterior interventricular sulcus and supplies smaller branches to both ventricles)

Answer 27

* anastomoses/connections between branches of the same coronary artery OR connections of branches of the RCA with branches of the left * epicardium contains more collateral vessels than endocardium * **Formed** through 2 processes: * **arteriogenesis:** new artery growth branching from pre-existing arteries * **angiogenesis:** growth of new capillaries within a tissue * growth is stimulated by shear stress (results from increased blood flow speed within and just beyond areas of stenosis) and by production of growth factors/cytokines (MCP-1 and VEGF) * formation may be impeded by diabetes due to increased antiangiogenic factor production

Answer 28

allows blood supply and oxygen to the myocardium that has become ischemic following gradual stenosis of one or more of the major coronary arteries (coronary artery disease) **basically, it's an alternative circulation** that allows for blood to still get to myocardium if main arteries are blocked

Answer 29

* where oxygen and other nutrients enter myocardium while waste products enter blood * at rest, heart extracts 50% to 80% of oxygen delivered to it * coronary blood flow is directly correlated with myocardial oxygen consumption

Answer 30

drains into cardiac veins (located alongside arteries; most venous drainage of heart occurs through veins in visceral pericardium) → great cardiac vein & coronary sinus (on posterior surface of heart in the coronary sulcus)

Answer 31

* myocardium has an extensive system of lymphatic capillaries and collecting vessels within layers of myocardium and valves * with cardiac contraction, lymphatic vessels drain fluid to lymph nodes in anterior mediastinum that empty into the superior VC * **protects myocardium against infection and injury**

Answer 32

**Location:** at junction of the RA and superior VC, just superior to the tricuspid valve **Innervation:** both sympathetic and parasympathetic nerve fibers **Discharge rate:** 60-100 action potentials per minute (depending on age and physical condition) **Effect:** action potential carried to AV node, as well as causing both atria to contract (beginning systole)

Answer 33

**Location:** right atrial wall superior to tricuspid valve and anterior to ostium of coronary sinus **Innervation:** autonomic parasympathetic ganglia that serve as receptors for vagus nerve and causing slowing of impulse conduction through AV node **Effect/Function:** conducts action potentials onwards to the ventricles

Answer 34

bundle of His (atrioventricular bundle) within posterior border of the interventricular septum

Answer 35

* thin and travels without much branching to the right ventricular apex * its thinness and relative lack of branches make it susceptible to interruption of impulse conduction by damage to the endocarium

Answer 36

* in some hearts, divides into two branches/fascicles * **Left anfterior bundle branch (LABB)** - passes left anterior papillary muscle and base of the LV and crosses aortic outflow tract * can be interrupted if there is damage to aortic valve or LV * **Left posterior bundle branch (LPBB)** - travels posteriorly, crossing left ventricular inflow tract to the base of the left posterior papillary muscle * spreads diffusely through posterior inferior LV wall * blood flow through here is non-turbulent so less injury/wear-and-tear

Answer 37

* terminal branches of the RBB and LBB * extend from the ventricular apexes to the fibrous rings and penetrate the heart wall to the outer myocardium * extensive network promotes rapid spread of the impulse to the ventricular apexes * activates interventricular septum first; basal and posterior portions last

Answer 38

depolarization repolarization

Answer 39

a) -80 to -90 mV b) -50 to -60 mV c) -60 to -70 mV

Answer 40

the point at which the cell membrane's selective permeability to these ions (Na+, K+, etc) is temporarily disrupted, leading to an “all or nothing” depolarization

Answer 41

hyperpolarization

Answer 42

* **Absolute:** period that follows depolarization in which no new cardiac action potential can be initiated by a stimulus; corresponds to time needed for reopening of channels that permit sodium and calcium influx into the cells * **Relative:** occurs near end of repolarization, following the effective/aboslute refractory period; membrane can be depolarized again if a greater-than-normal stimulus is applied

Answer 43

**P wave:** atrial depolarization **PR interval:** a measure of time from onset of atrial activation to onset of ventricular activation (depolarization) i.e. time necessary for electrical activity to travel from SA node through atrium, AV node, and His-Purkinje system to activate ventricular myocardial cells; normally 0.12 - 0.20 seconds **QRS complex:** sum of all ventricular muscle cell depolarization (normally 0.06 to 0.10 second) **ST interval:** when entire ventricular myocardium is depolarized **QT interval:** called "eletrical systole" of the ventricles - lasts ~0.4 seconds but varies inversely with HR **T wave:** ventricular repolarization

Answer 44

* property of generating spotaneous depolarization to threshold * enable SA and AV nodes to generate cardiac action potentials without any external stimulus * cells with this property aka **automatic cells** * Spontaneous depolarization is possible in these cells because their membrane potential does not actually “rest” during return to the resting membrane potential (they instead slowly depolarize toward threshold during diastolic phase of cardiac cycle - known as **diastolic depolarization)**

Answer 45

* Automatic cells of the cardiac conduction system can stimulate the heart to beat even when it is transplanted and thus has no innervation

Answer 46

* the regular generation of an action potential by the heart's conduction system * SA sets the pace (if fails, AV node takes over; but eventually conduction cells in the atria usually take over from the AV node) * Purkinje fibers have the slowest firing rate

Answer 47

* HR: the rate of impulse generation (firing), depolarization, and repolarization of myocardium * contractility: strength of atria/ventricle contraction

Answer 48

* increases electrical conductivity (thus HR) and the strength of myocardial contraction * increases myocardial performance * causes release of norepinephrine or circulating catecholamines which interact with β-adrenergic receptors on the cardiac cell membranes which increase influx of Ca++ and thus contractile strength * dilates coronary vessels by causing release of vasodilators

Answer 49

* affects heart through vagus nerve which releases acetylcholine * causes decreased HR and slows conduction through AV node

Answer 50

* long, narrow fibers with bundles of myofibrils, one nucleus (cardiac muscle), mitochondria, sarcoplasmic reticulum (internal membrane), sarcoplasm, sarcolemma (plasma membrane) * also has an external membrane system made of T tubules formed by inward pouching of the sarcolemma * looks striated due to light and dark bands of protein

Answer 51

d) all of the above are functions of cardiac muscle **a) transmit action potentials quickly from cell to cell** - via intercalated disks (3 junctions: desmosomes, fascia adherens, and gap junctions) **b) maintain high levels of energy synthesis** - lots of mitochondria so lots of ATP due to constant heart action **c) gain access to more ions (particularly sodium and potassium, in extracellular environment)** - cardiac fibers contain more T tubules than skeletal muscle, which gives them faster access to molecules needed for transmission of action potentials

Answer 52

* each myocardial sarcomere has myosin molecules (looks like two golf clubs - has an actin binding site and site of ATPase activity) * thick filaments of myosin overlap with thinner actin molecules to form **anisotropic/A band** (central dark band) * contraction results form myosin molecules heads (cross bridges) form force-generating bridges by binding with exposed actin molecules * **Isotropic/I bands:** only actin molecules, no myosin * **Z line:** dense fibrous structure at the center of each I band (thin filaments of actin extend from each side of the Z line) * **H zone:** center of sarcomere (and right in the middle of that is the **M line**)

Answer 53

* has 3 components: * **Troponin T:** aids in binding of troponin complex to actin and tropomyosin * **Troponin I:** inhibits ATPase of actomyosin * **Troponin C:** contains binding sites for calcium ions involved in contraction * Troponin T and I molecules release into bloodstream during myocardial injury (which can be used to measure if MI or damage has occurred) * when troponin and tropomyosin cover myosin binding sites on actin, cross-bridges release Ca++ and myocardium relaxes (basically it prevents contraction)

Answer 54

* a giant elastic protein in sarcomeres that attach myosin to the Z line and acts like a spring * influences myocardial stiffness and impacts myocardial diastolic filling

Answer 55

anaerobic metabolism (typically ATP is synthesized in mitochondria mainly from glucose, fatty acids, and lactate)

Answer 56

* expresses cardiac work, closely correlated with total cardiac energy requirements * deteremined by 3 major factors: * 1) amount of wall stress during systole (estimated by measuring SBP) * 2) duration of systolic wall tension (measured indirectly by HR) * 3) contractile state of myocardium (not measure clinically) * **increases:** with exercise * **Decreases:** with hypotension and hypothermia

Answer 57

70-75% (little O₂ left in reserve)

Answer 58

* cardiac muscle will take 70-75% of the oxygen from the coronary arteries BUT * O₂ content of the blood and amount of O₂ extracted from the blood cannot be increased under normal circumstances so if there are any increased energy needs, it can only be met by increasing coronary blood flow * When myocardial metabolism and consumption O₂ increases, concentration of vasoactive metabolic factors increase locally (adenosine, NO, prostaglandins) to dilate coronary arterioles → increase blood flow

Answer 59

**Definition:** change in developed tension at a given resting fiber length (basically it's the ability of the heart muscle to shorten) **Molecular level:** the thin filaments of actin slide over thick filaments of myosin (**cross bridge theory of muscle contraction);** sarcomeres shorten causing adjacent Z lines to move closer together * degree of shortening depends on the amount of overlap between the thick and thin filaments

Answer 60

* The procress by which an action potential arriving at the muscle fiber plasma membrane triggers the cycle (leading to cross-bridge formation and contraction) * activating the cycle depends on calcium availability * amount of force developed is regulated by how much the [Ca++] increases within the cardiomyocytes * calcium enters cell from IF after electrical excitation that increases clacium permeability → triggers release of additional calcium from storage sites (sarcoplasmic reticulum and tubule system) → binds with troponin

Answer 61

**L-type:** long lasting; these channels predominate and are the ones that get blocked by calcium channel-blocking drugs (verapamil, nifedipine, diltiazem) **T-type:** transient; much less abundant in the heart and are not blocked by ^ drugs

Answer 62

* **At resting state:** troponin I is bound to actin and tropomyosin molecule covers sites where myosins heads bind to actin (to prevent interaction between actin and myosin) * Calcium binds to troponin C (which results in tropomyosin moving troponin I to uncover binding sites on myosin heads) * Myosin and actin can now form cross-bridges (and ATP → ADP) * **Contraction:** sliding of thick and thin filaments over each other

Answer 63

* relaxation faciliated by calcium, troponin, and tropomyosin * Free calcium ions are actively pumped out of cell back into IF or back into storage * [Ca++] decreases in sarcomere, troponin releases its bound calcium * Tropomyosin complex moves and blocks active sites on actin molecule to prevent cross-bridge formation with myosin heads * **if relaxation is impaired, it can lead to increased diastolic filling pressures and eventually HF**

Answer 64

~5L/min (based on resting HR of 70 BPM and avg stroke volume of 70mL)

Answer 65

* **Definition:** amount of blood ejected per beat (in % form) * **Formula:** SV/EDV x 100% * **Normal values:** in men: ~58% +/- 8%; in women: 66% +/- 8% * **Factors:** * ****EF increases with factors that increase contractility (sympathetic NS activity) * EF decrease may indicate ventricular failure * Determined by echo, CT, nuclear medicine scane or cardiac catheter

Answer 66

1) preload 2) afterload 3) myocardial contractility 4) HR \*the first three affect stroke volume

Answer 67

**a) Cardiac output:** Unchanged; decreases (due to decrease in max HR) **b) HR:** slight decrease; increases less than in young people **c) Stroke volume:** Slight increase; no change **d) Ejection fraction:** unchanged; decreased **e) afterload:** increased; increased **f) EDV:** unchanges; increased **g) ESV (end-systolic volume):** unchanged; increased **h) Contraction:** decreased velocity; decreased **i) Myocardial wall stifness:** increased; increased **j) Max Oxygen consumption:** n/a; decreased **k) plasma catecholamines:** n/a; increased

Answer 68

* volume and pressure inside the ventricle at the end of diastole (**ventricular end-diastolic volume [VEDV]** and **pressure [VEDP]**) * Determined by 2 primary factors: * 1) amount of venous blood returning to ventricle during diastole (and venous return is dependent on blood volume and flow through venous system and AV valves) * 2) the amount of blood left in venrticle after systole (end-systolic volume) - ESV is dependent on strength of ventricular contraction and resistance to ventricular emptying * preload estimated by measuring the central venous pressure (CVP) for the right side of the heart and pulmonary artery wedge pressure for left side (left atrial pressure) * Normal values: CVP (1-5mmHg); pulmonary artery wedge pressure (4-12mmHg)

Answer 69

states that wall tension generated in the wall of the ventricle (or any chamber/vessel) to produce a given intraventricular pressure, depends directly on ventricular size or internal radius and inversely on ventricular wall thickness * i.e. VEDV (ventricular end-diastole volume) determines size of ventricle and stretch of muscle fibers therefore affects tension/force for contraction The larger the vessel radius, the larger the wall tension required to withstand a given internal fluid pressure. For a given vessel radius and internal pressure, a spherical vessel will have half the wall tension of a cylindrical vessel.

Answer 70

* represents the relationship between stroke volume and end diastolic volume * indicates that the volume of blood in the heart at the end of diastole (i.e. the volume determines length of its muscle fibers) is directly related to force of contraction during next systole * i.e. the larger the volume of blood flowing into ventricle, the greater the force of contraction (but to an extent where stretching muscle fibers beyond the optimal length will lead to decreased SV)

Answer 71

a) increases SV (and thus increases CO, stroke work) b) SV decreases (may also cause increases in VEDP which may lead to HF and pressures to back up into venous and pulmonary circulation = pulmonary or peripheral edema)

Answer 72

* resistance to ejection of blood from the LV (the load the muscle must move during contraction) * Determined by: aortic pressure and TPR * aortic systolic pressure is an index of afterload (pressure in ventricle must exceed aortic pressure before blood can pumped out during systole) * Decreased afterload (low aortic pressures) allow heart to contract more rapidly and efficiently * Increased afterload (high aortic pressures) slow contraction and cause higher workloads for the heart to pump against to eject blood * the most sensitive measure of afterload is SVR

Answer 73

* aka total peripheral resistance (TPR) * causes increased aortic pressure * in those with HTN, increased SVR means aferload is chronically elevated, resulting in increased ventricular workload and myocardial hypertrophy

Answer 74

volume of blood ejected per beat during systole

Answer 75

**1) Changes in the stretching of the ventricular myocardium caused by changes in VEDV (preload)** - increased venous return distends ventricle which increases preload → increases SV → increases CO up to a certain point (excess preload will decrease SV) **2) Alterations in inotropic stimuli of the ventricles** - most important ones are epinephrine and norepinephrine released from SNS * other +ve inotropes: thyroid hormone, dopamine * -ve inotropes: acetylcholine **3) Adequacy of myocardial oxygen supply** - levels of oxygen and CO2 in coronary blood influence contractility * severe hypoxemia (O2 sat \< 50%), contractility is decreased * less severe hypoxemia (O2 sat \>50%), contractility is stimulated * mod degrees of hypoxemia - may increase contractility by enhancing myocardial response to circulating catecholamines

Answer 76

a) lower HR b) higher SV c) lower peripheral resistance

Answer 77

1) CNS 2) ANS 3) neural reflexes 4) atrial receptors 5) hormones

Answer 78

**Location:** in the brainstem (medulla and pons) with additional areas in hypothalamus, cerebral cortex, and thalamus **Function:** influnce firing rate of SA node (sympathetic and parasympathetic activity) * hypothalamic centers regulate CV responses to changes in temp * cerebral cortex centers adjust cardiac reaction to a variety of emotional states * brainstem control center regulates HR and BP

Answer 79

**Location:** aortic arch and carotid arteries **Function:** influences short term regulation of vascular smooth muscle of resistance arteries, myocardial contractility, and hear rate (all components of BP control) * If BP decreases, baroreceptor reflex accelerates HR, increases myocardial contractility, and increases vascular smooth muscle contractions in arterioles, which all raise BP * If BP increases, baroreceptors increase rate of discharge, sending neural impulses over a branch of the glossopharyngeal nerve (CN IX) and through the vagus nerve to the cardiovascular control centers in the medulla → increases parasympathetic activity & decrease sympathetic activity (resistance arteries to dilate, decrease HR and contractility) * **reflex is CRITICAL to maintaining adequate tissue perfusion**

Answer 80

**Location:** they are mechanoreceptors that are in both atria (located where veins, venae cavae, and pulmonary veins enter their respective atria) **Function:** stimulation of atrial receptors increase urine volume (presumably due to reeduction in ADH) * atrial natriuretic peptides also released which have diuretic and natriuretic (salt excretion properties) to lead to decreased blood volume and pressure; amy also relax vascular smooth muscle and oppose myocardial hypertrophy

Answer 81

when the heart rate increases in response to a rise in atrial pressure (i.e increase in blood volume); changes in HR that may occur after IV infusions of blood or other fluid thought to be caused by reflex mediated by atrial volume receptors that are innervated by vagus nerve (volume receptors thought to respond to increased plasma volume)

Answer 82

* hormones/biochemicals can affect all parts of the blood vessels * **Norepinephrine** (mainly released as a NT from the adrenal medulla) dilates vessels of liver and skeletal muscle, causes increase in myocardial contractility * **Thyroid hormones:** enhance sympathetic activity and increase cardiac output * **Growth hormone:** works with insulin-like growth factor 1 (EGF-1) to increase myocardial contractility * decreases in thyroid hormone or growth hormone levels may result in bradycardia (\<60), reduced cardiac output, and low BP

Answer 83

describes the part of the systemic cirulation that supplies the skin and extremities, particularly legs and feet

Answer 84

1) tunica intima (innermost layer) 2) tunica media (middle/medial layer) 3) tunica externa/adventitia (outermost layer) - also contains nerves and lymphatic vessels and then lumen is the inside \*note: blood vessel walls vary in thickness depending on thickness/absence or one or more of these three layers

Answer 85

vasa vasorum

Answer 86

* thick-walled pulsating blood vessel transporting blood away from the heart * in systemic circulation, arteries carry oxygenated blood * composed of elastic connective tissue, fibrous connective tissue, and smooth muscle fibers

Answer 87

**Structure:** thick tunica media with more elastic fibers than smooth muscle fibers (ex. aorta, trunk of pulmonary artery) **Function:** elasticity allows vessel to absorb energy and stretch as blood is ejected from heart during systole

Answer 88

**Structure:** medium and small size arteries; farther from the heart than elastic arteries; contain more muscle fibers and fewer elastic fibers than elastic arteries **Function:** * distribute blood to arterioles throughout the body * blood flow control and directing flow to body parts that need it the most (because their smooth muscle can contract/relax) - vasoconstriction/vasodilation

Answer 89

**Structure:** artery becomes an arteriole where diameter of its lumen narrows to \<0.5mm; mainly composed of smooth muscle **Function:** regulate blood flow into capillaries by constricting/dilating to slow or increase blood flow into the capillaries * thick smooth muscle layer of arterioles is a major determinant of resistance blood encounters as it flows through the systemic circulation

Answer 90

metarterioles (**Structure:** discontinuous smooth muscle cells in tinuca media) "true" capillaries (**Structure:** no smooth muscle cells; a layer of endothelial cells surrounded by a basement membrane; some capillaries have endothelial cells with pores/**fenestrations)**

Answer 91

**Structure:** ring of smooth muscle at the point where capillaries branch from metarterioles **Function:** sphincters contract and relax to regulate blood flow through capillary beds; helps to maintain arterial pressure and regulate selective flow to vascular beds

Answer 92

* thin walls (one layer thick) and unique structure allow for rapid exchange * exchange of: * water * small (low molecular weight) soluble molecules * some larger molecules (albumin) * cells of innate and adaptive components of immune system between blood and IF * Substances pass through capillary lumen and IF via: * 1) through junctions between endothelial cells * 2) through fenestrations in endothelial cells * 3) in vesicles moved by active transport across endothelial cell membrane * 4) via diffusion through endothelial cell membrane

Answer 93

a single capillary: 0.5 - 1mm in length, 0.01mm in diameter BUT so numerous that their total surface area may be more than 600m²

Answer 94

endothelial cells

Answer 95

1) **substance transport** - via vesicles, opening of tight junctions, across cytoplasm 2) **coagulation** 3) **antithrombogenesis** - endothelial surface is normally antithrombic and maitains balance between pro- and anticoagulant factors 4) **fibrinolysis** 5) **immune system function** - expresses chemotactic agents and adhesion molecules that support WBCs moving into tissues 6) **tissue and vessels growth and wound healing** - release growth factors 7) **vasomotion** (vascular dilation via production of NO, prostacyclin, vasodilators; vascular constriction via production of endothelin-1, angiotensin II) 8) **Lipid metabolism** - expresses receptors for lipoprotein lipase and LDLs

Answer 96

**Structure:** thin walled with more fibrous connective tissue, have larger diameter and more numerous than arteries; highly distensible * smallest venules downstream from capillaries have an endothelial lining and are surrounded by connective tissue * largest venules have some smooth muscle fibers in their thin tunica media * have less elastic tissue than that in arteries so veins do not recoil as much or as rapidly after distention * receive nourishment from vasa vasorum **Function:** facilitate one-way flow of blood toward heart (via valves, which are made of tunica intima) and to prevent backflow and blood pooling

Answer 97

When a person stands up, skeletal muscles contract to compress deep veins of the legs and assist flow of blood toward the heart **Muscles relaxed:** when pressure from volume of blood downstream is enough to push valves open, allow blood to move back to heart **Muscles contracted:** when pressure below the valve drops causing blood to start backflow but causes the valves to close; muscles then contract to assist in return of desoxygenated blood to RA

Answer 98

amount of fluid moved per unit of time (usually L/min or mL/min) Factors influencing blood flow: **pressure\*, resistance\*,** velocity, turbulent vs. laminar flow, and compliance

Answer 99

* force exerted on the liquid per unit area, clinically expressed as mmHg or torr (1 torr = 1 mmHg) * blood flow to an organ depends partly on pressure difference between arterial and venous vessels supplying that organ (moves from higher to lower pressure)

Answer 100

* opposition of blood flow (which typically results from diameter and length of vessels) * changes in blood flow through an organ results from changes in vascular resistance within the organ bc of increases/decreases in vessel diameter and opening/closing of vascular channels * resistance in vessel is inversely related to bloow flow (↑ resistance = ↓ blood flow) * resistance is determined by radius and length of blood vessel and by blood viscosity (**radius/diameter** the most important factor in determining resistance in a single vessel)

Answer 101

indicates that resistance is directly related to tube length and blood viscosity, and inversely related to radius of the tube to the fourth power (r⁴) so: * ↑ viscosity = ↑ resistance * ↑ length = ↑ resistance * ↑ radius = ↓ resistance the flow (Q) of fluid is related to a number of factors: the viscosity (n) of the fluid, the pressure gradient across the tubing (P), and the length (L) and diameter(r) of the tubing

Answer 102

remember formula for Poisueille's law: R = 8ηℓ/(πr⁴ ) 1. **Viscosity:** polycythemia, dehydration 2. **Length:** increased body weight/height 3. **Radius** (r⁴): Vasoconstriction (increase in SNS, decrease in vessel diameter)

Answer 103

remember formula for Poisueille's law: R = 8ηℓ/(πr⁴ ) 1. **Viscosity:** anemia 2. **Length:** decreased body weight/height 3. **Radius** (r⁴): Vasdodilation (decrease in SNS, increase in vessel diameter)

Answer 104

* resistance to flow through a system of vessels * depends on individual vessel characteristics and whether the vessels are arranged in series or in parallel and on the total cross-sectional area of the system * vessels arranged in parallel provide less resistance than those in series * more resistance in blood flow through distributing arteries than in capillary bed itself

Answer 105

* distance blood travels in a unit of time (cm/sec) * directly related to blood flow (amount of blood moved per unit of time) and inversely related to the cross-sectional area of the vessel in which blood is flowing * as blood moves from aorta → capillaries, total cross-sectional area of vessels increases and velocity decreases * increased total cross sectional area (by branching of aterial vessels) reduces flow rate

Answer 106

**Laminar:** concentric layers of molecules move "straight ahead" with each layer flowing at slightly different velocity * cohesive attraction occurs between fluid and vessel wall - prevents blood molecules that are in contact with the wall from moving at all * next thin layer of blood is able to slide slowly past stationary layer and so on until, at the center, blood velocity is greatest * larger vessels have larger center layer (i.e. less resistance to flow; greater slow and velocity than smaller vessels) **Turbulent:** where flow is obstructed, the vessel turns, or blood flows over rough surfaces (whorls and eddy currents produce noise i.e. murmur that is head on auscultation) * resistance increases with turbulence (frequently in areas with plaque build up)

Answer 107

* the increase in volume a vessel can accommodate for a given increase in pressure * Depends on nature of vessel wall (such as the ratio of elastic fibers to muscle fibers in the wall) * elastic arteries more compliant than muscular arteries * veins more compliant than either type of artery (serve as storage areas for circulatory system) * determines a vessel's response to pressure changes (ex. venous system can hold large volume of blood with only small increase in pressure VS. arterial system is less compliant where small changes in blood volume can significantly change in arterial pressure)

Answer 108

cardiac output x peripheral resistance (BP = CO x TPR) if arterial pressure (or MAP) drops/increases, arteriolar blood flow also follows in the same direction

Answer 109

**Systolic BP:** highest arterial blood pressure following ventricular contraction or systole **Diastolic BP:** lowest arterial blood pressure that occurs during ventricular iflling or diastole **Mean arterial pressure (MAP):** average pressure in the arteries through the cardiac cycle, depends on the elastic properties of the arterial walls and mean volume of bloow in the arterial system

Answer 110

difference between the systolic pressure and diastolic pressure (P_s - P_d) normal range: 40 to 50 mmHg; directly related to arterial wall stiffness and stroke volume

Answer 111

HR x SV **Increase in CO** (without change in peripheral resistance) causes ↑ MAP and flow rate which means ↑ blood flow to arterioles **Decrease in CO** (again without change in peripheral resistance) causes ↓ MAP and arteriolar flow

Answer 112

**Definition:** total resistance in the systemic circulation; primarily a function of arteriolar diameter **Increased TPR (**with CO remaining constant): arteriolar constriction raises MAP by reducing blood flow into capillaries **Decreased TPR** (with CO remaining constant): arteriolar dilation decreases MAP by allow more blood flow into capillaries

Answer 113

1) sympathetic stimulation of heart, arterioles, and veins 2) parasympathetic stimulation of heart CV center in the medulla receives input from arterial baroreceptors and chemoreceptors throughout vascular system and then modifies vagal and sympathetic output to control HR and contractility + vascular diameter Vasoconstriction is regulated by an area in brainstem that maintains constant (tonic) output of norepinephrine from sympathetic fibers in peripheral arterioles. NEEDED and essential for maintaining BP

Answer 114

**Baroreceptors:** stretch receptors located predominantly in aorta and carotid sinus; respond to changes in smooth muscle fiber length by altering their rate of discharge and supply sensory info to the CV center in brain stem * when activated (stretched), baroreceptors decrease CO by lowering HR and SV and peripheral resistance ⇒ ↓ BP **Arterial chemoreceptors:** located in aortic arch and carotid arteries; sensitive to [O₂], [CO₂], and pH * most important in resp control but also transmit impulses to medullary cardiovascular centers that regulate BP * decrease in arterial oxygen concentration (hypoxemia), an increase in arterial PaCO₂ concentration, or to a lesser extent a decrease in arterial blood pH causes a reflexive increase in HR, SV, and BP

Answer 115

Through their effects on vascular smooth muscle and blood volume (constricting or dilating arterioles in organs), which can: 1) increase/decrease flow in response to body's needs 2) redistribute blood volume during hemorrhage or shock 3) regulate heat loss

Answer 116

**Vasoconstrictors:** * **angiotensin II\*** - however no major role in BP control under normal circumstances * vasopression (ADH) - no major role in BP control under normal circumstances * **epinephrine\*** * **norepinephrine\*** \*part of renin-angiotensin-aldosterone system **Vasodilators:** * atrial natriuretic hormones * not key but also present: adrenomedullin (ADM) - vasodilating peptide

Answer 117

**Epinephrine** * catecholamine hormone released from adrenal medulla * causes casoconstriction in most vascular beds except coronary, liver, and skeletal muscle circulations **Norepinephrine** * mainly acts as a NT but some also released from adrenal medulla * when released into circulation, it is more potent vasoconstrictor than epinephrine

Answer 118

* by increase blood volume through their influence on fluid reabsorption of water from tubular fluid distal tubule and collecting duct * Aldosterone stimulates reabsorption of sodium, chloride, and water * vasopressin (ADH) mechanism and RAAS tend to increase water, sodium, and chloride retention (increasing total plasma volume)

Answer 119

* atrial natriuretic peptide (ANP), B-type natriureitc peptide (BNP), C-type natriuretic peptide (CNP), and urodilatin * vasodilators AND regulators of Na+ and H₂O excretion (diuresis and natriuresis) * increased pressure or diastolic volume stimualtes release of peptide hormones which antagonize volume retention mechanisms by promoting water, sodium, and chloride loss = decrease in total plasma volume * ↑ BNP levels predict increased risk of poor outcome for HF, PE, valvular heart disease, and chronic CAD

Answer 120

* aka endothelium-derived relaxing factor (EDRF) * an intercellular/intracellular signaling molecule produced in endothelial cells * various roles in vascular function * vasodilator * inhibitor of smooth muscle proliferation * This is why sublingual nitroglycerin is beneficial for coronary artery spasms!

Answer 121

* vasodilator peptide present in lots of tissues * unclear role but has numerous cardiovascular effects

Answer 122

* family of three peptides (ET-1, ET-2, and ET-3) and four receptors produced in cells in vascular smooth muscle (endothelium) kidneys and other organs * endothelin binding to type A receptor causes vasodilation and natriuresis * endothelin binding to type B receptor causes OPPOSITE reponse - vasoconstriction + sodium/water retention * inhibitors of ET-1 used for pulmonary HTN tx

Answer 123

* vasodilator produced by actions of cyclooxygenases (COX-1 and COX-2) on arachidonic acid * other properties: antithrombotic (opposing clot formation), decreasing platelet activity, inhibiting release of growth factors from macrophages and endothelial cells * Nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit these cyclooxygenases have been associated with CV disease risk in healthy people and in those with a known CV disease.

Answer 124

1) volume of fluid within the veins 2) compliance (distensibility) of the vessel walls

Answer 125

venous: 66%; 10 arterial: 11%, 100 the remainder of the blood volume is within the heart, capillaries, and pulmonary circulation

Answer 126

* sympathetic NS (veins are highly innervated by sympathetic fibers that control venous smooth muscle) * smooth muscle contraction in the veins result in stiffening in vessel walls (which reduces venous distensibility and increased venous BP (forcing more blood through the veins and into right heart)

Answer 127

**1) Skeletal muscle pump:** when skeletal muscles contract, veins within the muscles are partially compressed cause decreased venous capacity and increased return to the heart **2) Respiratory pump:** acts during inspiration, when veins of abdomen are partially compressed by downward movement of the diaphragm (increasde abdo pressure moves blood toward the heart)

Answer 128

directly; inversely

Answer 129

the difference between pressure in the aorta and pressure in coronary vessels (∴ aortic pressure drives pressure for arteires and arterioles that perfuse myocardium) vasodilation/constriction maintain coronary blood flow despite stresses imposed by constant contraction and relaxation of heart muscle and despites physiologic shifts of coronary perfusion pressure

Answer 130

* Systolic compressive effect occurs when coronary arteries are compressed by ventricular contraction * also the aortic valve cusps obstruct coronary blood flow by occluding the openings of the coronary arteries during systole * so during this period of time (systole) when coronary blood flow is slow of stopped, **myoglobin** (protein in heart muscle that binds oxygen) provides the oxygen supply to myocardium (and then their oxygen levels are replenished during diastole)

Answer 131

* automatic self-regulation * enables organs to regulate blood flow by altering resistance (diameter) in their arterioles * Autoregulation in coronary circulation maintains blood flow at a nearly constant rate at perfusion pressures between 60 to 140 mmHg (while other influencing factors are held constant) ⇒ ensures constant coronary blood flow despite shifts in perfusion pressure

Answer 132

* during regular activity, coronary blood flow is regulated locally by factors that cause autoregulation * **during exercise,** β2-receptors on smaller coronary resistance arteries have vasodilating effects which allow for ~25% increase in blood flow; at the same time, α-adrenergic receptors in larger arteries cause vasoconstriction to direct the blood flow to the inner layers of the myocardium

Answer 133

* one-way network of lymphatic vessels and the lymph nodes that is important for immune function, fluid balanace, and transport of lipids, hormones, and cytokines * 3L of fluid is filtered daily out of venous capillaries in body tissues and not reabsorbed (turns into lymph and is then carried by lymphatic vessels to the chest where it enters venous circulation) * lymphatic vessels run in same sheaths with arteries and veins * no pumps in this system; valves are used to ensure one-way flow of excess IF (i.e. now lymph) toward the heart

Answer 134

* consists primarily of water and small amounts of dissolved proteins (mostly albumin) that are too large to be reabsorbed into the less permeable blood capillaries * carries lymphocytes and antigen-presenting cells * APCs are carried to next lymph node * lymphocytes traffic between lymph nodes

Answer 135

**lympathic venules** and **veins** → drains into one of two large ducts in thorax (**right lympathic duct** and **thoracic duct** → drains into **right** and **left subclavian veins** (respectively) * right lymphatic ducts drains lymph from R arm and R side of head and thorax * larger thoracic duct receives lymph from rest of the body

Answer 136

**Structure:** thin walled veins; in larger lymphatic veins, endothelial flaps form valves similar to those in veins carrying blood **Function:** valves allow lymph to flow one way as lymphatic vessels are compressed intermittenetly by skeletal muscle contraction, pulsatile expansion of the artery in the same sheath, and contraction of the smooth muscles in the walls of the lymphatic vessels

Answer 137

Lymph nodes * lymph enters nodes via **afferent lymphatic vessels,** filters through sinuses in the node, and leaves via **efferent lymphatic vessels** * lymph flows slowly through nose to allow phagocytosis of foreign material within node and to deliver lymphocytes

Answer 138

**Description:** veins in which blood has pooled, producing distended tortuous and palpable vessels **Causes:** 1) trauma to saphenous veins that damages one or more valves or 2) gradual venous distention caused by gravity on blood in the legs **Pathophysiology:** typically involve saphenous veins of the leg * when valve is damaged, a section of the vein is subjected to pressure of a larger volume of blood under the influence of gravity * vein swells as it becomes engorged and surrounding tissue becomes edematous (due to ↑ hydrostatic pressure pushing plasma through stretched vessel wall and increased vessel wall permeability) * pressure eventually damages venous valves - unable to maintain normal venous pressure **Risk/Contributing factors:** venous distention developing over time in those who stand for long periods, wear constricting garments, cross legs at knees (diminishes muscle pump action) * Other risk factors: age, female, family hx of varicose veins, obesity, pregnancy, DVT, previous leg surgery **Treatment:** starts conservatively (excellent wound healing) - leg elevation, compression stockings, exercise * Invasive tx: endovenous ablation, sclerotherapy or surgical ligation, conservative vein resection, vein stripping

Answer 139

Chronic Venous Insufficiency (CVI)

Answer 140

**Description:** inadequate venous return over a long period **Causes:** Progression of varicose veins and valvular incompetence (over long period of time) **Pathophysiology:** venous HTN, circulatory stasis, and tissue hypoxia cause inflammatory rxn in vessels and tissue leading to fibrosclerotic remodeling of skin and then ulceration **Sx:** * edema of LE and hyperpigmentation of skin on feet and ankles (may extend to knees) * skin colour and texture changes * sluggish circulation to extremities leading to nutrient/waste/oxygen exchange demands to not be met so trauma/pressure can lower oxygen supply and cause cell death and necrosis (**venous stasis ulcers**), cellulitis * infection (during or even after repair surgery due to sluggish circulation) **Treatment:** * starts conservatively (excellent wound healing) - leg elevation, compression stockings, exercise * Invasive tx: endovenous ablation, sclerotherapy or surgical ligation, conservative vein resection

Answer 141

**Thrombus:** Blood clot that remains attached to a vessel wall **Thromboembolus:** a detached thrombus * venous thrombi are more common than arterial thrombi because flow and pressure are lower in veins

Answer 142

**Description:** occurs when a blood clot forms in a deep vein, primarily in lower extremity **S/S:** usually asymptomatic and difficult to detect clinically **Diagnosis:** as mentioned ^, difficult to detect but if thrombosis does occur, dx is confirmed by a combination of serum D-dimer measure (fibrin degradation product) and Doppler ultrasonography **Treatment:** if untreated, high risk of embolization of a part of the clot to the lung (pulmonary embolism) * PREVENTION! → early ambulation, pneumatic devices, prophylactic anticoagulation * Management: anticoagulation therapy (low MW heparin; warfarin, & factor Xa inhibitors and direct thrombin inhibitors which are newer) * potentially thrombolytic therapy/placement of IVC filter for some people

Answer 143

Three factors: * 1) **venous stasis** (immobility, age, CHF) * 2) **venous endothelial damage** (trauma, IV meds) * ortho trauma/surgery, SCI, and ob/gyn conditions can be associated up to 100% likelihood of DVT * 3) **hypercoagulable states** (inherited disorders, malignancy, pregnancy, use of oral contraceptives or hormone replacement therapy) * ex. factor V Leiden mutation, prothrombin mutations, deficiencies in protein C, protein S, and antithrombin * commonly found in those who develop thrombi in absence of usualy risk factors known as the **triad of Virchow**

Answer 144

* formed from accumulation of clotting factors and platelets (often near a venous valve) * inflammation around the thrombus promotes further platelet aggregation and thrombus propagates and grows proximally * may cause pain and redness but if vein is deep, usually not accompanied by S/S * if thrombus causes ++obstruction to venous blood flow, edema in extremity occurs (from increased pressure in vein behind clot) * Most will dissolve without treatment * Persistent venous obstruction may lead to chronic venous insufficiency and post-thrombotic syndrome (with associated pain, edema, and ulcer in affected limb)

Answer 145

**Description:** progressive occlusion of superior vena cava (SVC) leading to venous distention in UE and head **Causes:** bronchogenic cancer (75% of cases) followed by lymphomas and metastasis of other cancers * less common: TB, mediastinal fibrosis, CF * 40% of cases associated with: invasive therapies (pacemaker wires, central venous catheters, and pulmonary artery catheters) **Pathophysiology:** SVC is relatively low pressure vessel so tissue expansion/lesions that occupy space can easily compress it, as well as presence of cancers in the bronchus (because R mainstem bronchus is right beside SVC) * SVC is also surrounded by lymph nodes and lymph chains that commonly become involved in thoracic cancers and compress SVC during tumor growth * onset of SVCS is slow, so collateral (alternative pathway if SVC is blocked) venous drainage to the azygos vein has time to develop **Clinical Manifestations:** edema & venous distention in UE and face (including ocular beds) * complaints of feeling of fullness in head or tightness of shirt collars, necklaces, and rings * cerebral edema may cause headache, visual disturbance, impaired consciousness * face and arms skin purple and taut * prolonged cap refill * respiratory distress (potentially) due to edema of bronchial structures/compression of bronchus by cancer * in infants, SVCS can lead to hydrocephalus **Diagnosis:** chest X-ray, Dopper studies, CT, MRI, ultrasound; generally not a vascular emergency because of slow onset and collateral venous draining **but it is an oncologic emergency** **Treatment:** * _If from cancer:_ radiation, chemo, surgery, use of diuretics, steroids, and anticoagulants * _If not from cancer:_ bypass surgery using various grafts, thrombolysis, baloon angioplasty, intravascular stents

Answer 146

* consistent elevation of systemic arterial blood pressure (defined as sustained SBP of 140+ mmHg or DBP of 90+ mmHg) * results from a sustained increase in peripheral resistance (arteriolar vasoconstriction), an increase in circulating blood volume, or both * most common primary diagnosis in the US * chance of developing primary HTN increases with age * prevalence is higher in African Americans, and in those with diabetes * those with elevated BP are at risk of developing HTN unless lifestyle mods/tx occurs * all stages of HTN are associated with increase risk for target organ disease events (MI, kidney disease, stroke)

Answer 147

**Primary:** most cases (92-95%) - essential or idiopathic HTN **Secondary:** caused by an underlygin disorder (such as renal disease) - 5 to 8% of cases

Answer 148

* combo of genetic and environmental factors * Genetic-related: epigenetic changes influenced by diet and lifestyle * Risk factors: * **family hx** * **aging** * **cigarette smoking** * **obesity** - can cause changes in adipokins (leptin, adiponectin) and associated with icnreased activity of SNS and RAAS * **heavy alcohol consumption** * **gender** (men \> women before 55; women \> men after 55) * **black race** * **high dietary sodium intake** * **low dietary intake of potassium, calcium, magnesium** (because without intake of these, sodium retention occurs; these are needed for natriuretic peptides to function normally to regulate sodium) * **glucose intolerance**

Answer 149

* result of a complex interaction between genetics and environment mediated by host of neurohumoral effects (these effects are mediated by SNS, RAAS, and natriuretic peptides) * inflammation, endothelial dysfunction, obesity-related hormones and insulin resistance all contribute to increased peripheral resistance and increased blood volume * those with HTN secrete less salt in urine (**pressure-natriuresis relationship**) * **SNS:** increases HR and systemic vasoconstriction thus raising BP; SNS also causes vascular remodeling, renal Na+ retention, insulin resistance, and increased renin and angiontensin levels, and procoagulant effects * **RAAS:** overactivity of this system contributes to salt and water retention and increased vascular resistance * _angiotensin II_ mediates **arteriolar remodeling** changing vessel wall resulting in permanent increase in peripheral resistance * angiontensin II also associated with end-organ effects of HTN * _adolsterone:_ sodium retention, insulin resistance

Answer 150

It opposes the activity of the RAAS which has multiple components that contribute to incresed peripheral resistance therefore increased BP (hypertension)

Answer 151

**1) Release of renin, synthesis of angiotensin II through ACE, stimulate of AT1 receptor, and secretion of aldosterone** * Abnormal amounts of Ang II contributes to insulin resistance, blood vessel remodeling, atherogenesis, and decreased release of endothelial vasodilators and anticoagulants * in the heart, Ang II and aldosterone contribute to hypertensive hypertrophy and fibrosis of heart muscle, decreased contractility, and icnreased susceptibility to arrhythmias and heart failure * in kidneys, will cause shifts in sodium excretion and cause renal fialure * Drugs that block RAAS: ACE inhibitors, direct renin inhibitors, ARBs, and aldosterone inhibitors are used to manage HTN, MI, and HF to lower BP and protect CV function **2) counterregulatory system -** vasodilatory, antiproliferative, antifibrotic, and antithrombic effects * Synthesis of angiotensin 1-7 from Ang II which stimulates Mas receptors in various organs * protective effects result in lower BP, less vascular inflammation and clotting, and decreased tissue remodeling and damage to target organ tissues * protects renal tissue * improves insulin sensitivity in those with diabetes and HTN

Answer 152

* those nutrients are needed for natruietic hormones to functio properly * dysfunction of these hormones contributes to increased vascular tone and shift in pressure-natruiretic relationship * inadequate natruietic function leads to increased serum levels of said peptides (which in HTN, increased ANP and BNP levels are linked to an increased risk of ventricular hypertrophy, atherosclerosis, and HF) * salt retention leads to water retention = increased blood volume = increased BP * subtle renal injury results (with renal vasoconstriction and tissue ischemia) * causes inflammation of kidney and dysfunction - promotes additional sodium retention

Answer 153

* Peripheral vascular resistance-mediated ischemic cellular injury and the release of **damage-associated molecular patterns (DAMPs)** that activate Toll-like receptors on immune cells * activation of innate/adaptive immunity results in damage to endothelial cells → long term inflammation eventually leads to decreased vasodilator production, vascular remodeling and smooth muscle contraction; also contributes to insulin resistance, decreased natriuresis, and autonomic dysfunction (increased SNS activity)

Answer 154

* obesity contributes to adipocyte dysfunction and ectopic fat deposition throughout CV system * dysfunctional adipocytes release inflmamtory mediators that contribute to vascular remodeling and endothelial dysfunction with decreased endogenous vasodilator release * lead to high levels of leptin (released by adipocytes) which increased SNS activity, decrease sodium excretion, promote inflammation, and stimulate myocyte hypertrophy * adiponectin is reduced in obesity - associated with insulin resistance, decreased vasodilator production, activation of SNS, and RAAS * obesity-related changes result in vasoconstriction, salt and water retention, and renal dysfunction that may contribute to the development of hypertension. * Obesity also is linked with insulin resistance, which contributes to vascular dysfunction and the development of sustained hypertension.

Answer 155

* insulin resistance associated with decreased endothelial release of NO and other vasodilators * also affects renal function and causes renal salt and water retention * insulin resistance is associated with overactivity of SNS and RAAS

Answer 156

* caused by underlying disease proces or medication that raises peripheral vascular resistance or CO * ex. renal vascular or parenchymal disease, adrenocortical tumors, adrenomedullary tumors (pheochromocytoma), and drugs (oral contraceptives, corticosteroids, antihistamines) * if the cause is identified and removed before permanent structural changes occur, BP returns to normal

Answer 157

Chronic hypertensive damage to blood vessels and tissues leading to target organ damage in the heart, kidney, brain, and eyes

Answer 158

* hypertrophy 2' to HTN is mediated by catecholamines from SNS and angiotensin II * hypertrophy is characterized by changes in myocyte proteins, apoptosis of myocytes, and deposition of collagen in heart muscle * causes heart to thicken, scar, and less able to relax during diastole leading to HR with preserved ejection fraction * increased heart muscle size increases oxygen demand delivery over time, impaired heart contractility, and increased risk of MI, HR with reduced ejection fraction * **Cardiovascular complications:** left ventricular hypertrophy, angina pectoris, heart failure, CAD, MI, sudden death * **Vascular complications:** formation, dissection, and rupture of aneurysms; atherosclerosis leading to vessel occlusion * **Renal complications:** parenchymal damage, nephrosclerosis, renal arteriosclerosis, renal insufficiency or failure * **Retina complications:** retinal vascular sclerosis, exudation, hemorrhage * **Cerebrovascular complications:** TIAs, stroke, cerebral thrombosis, aneurysm, hemorrhage, dementia

Answer 159

**Description:** rapidly progressive HTN which DBP is usually \> 140mmHg; can occur in those with primary HTN **Cause:** uncertain about why some get this complication and others don't; others: complications with pregnancy, cocain or amphetamine use, reaction to certain meds, adrenal tumors, and alcohol withdrawal **Pathophysiology:** high arterial pressures cause cerebral arterioles incapable of regulating blood flow to the cerebral capillary beds; high hydrostratic pressures in capillaries cause vascular fluid to excude into interstitial space * if pressure is not reduced, cerebral edema and dysfunction (encephalopathy) increase until death occurs * can cause papilledema, cardiac failure, uremia, retinopathy, CVA **Clinical Manifestations:** * *Early Stages:* no clinical manifestations other than elevated BP (silent disease) - may begin to accelerate its effects on tissues if not detected/treated * most S/S are caused by complications that damage organs and tissues outside vascular system and share in common elevated BP as a symptom∴ S/S also are organ-/tissue-specific **Diagnosis:** measurement of BP on at least two separate occasions, averaging two readings at least 2 minutes apart (person is seated, arm supported at heart level, person must be at rest for 5+ minutes, and should not have smoked/ingested any caffeine in the previous 30 minutes) * 24 h BP monitoring, CBC, urinalysis, biochemical blood profile, ECG **Treatment:** depends on severity * liefstyle mods (exercise, diet, smoking cessation, weight loss) * reducing salt intake * Medications: thiazide diuretics (alone) or with ACE inhibitors/ARBs or calcium channel blockers

Answer 160

**Description:** decrease in SBP of at least 20 mmHg or decrease in DBP of at least 10 mmHg within 3 minutes of moving to a standing position **Etiology:** Idiopathic/primary OH - unknown initial cause (usually called neurogenic and is the result of primary neurologic disorders or secondary to conditions that affect autonomic function **Prevalence/Incidence:** affects men \> women; usually 40 - 70 y.o.; up to 18% of elderly may be affected with primary OH **Pathophysiology:** Typically upon standing, gravitational changes on circulation are compensated by increased sympathethic activity via mechanisms like baroreceptor-mediated reflex arteriolar and venous constriction and increased HR; closing of valves in venous system; contraction of leg muscles; and decrease in intrathoracic pressure (∴ maintaining BP) **but these mechanisms are dysfunctional/inadequate in those with OH** (resulting in blood pooling upon standing and normal arterial pressure not maintained) * can be acute or chronic * **Acute:** elderly are particularly susceptible to this one; caused when normal regulatory mechanisms are sluggish due to: * altered body chemistry * drug action (antihypertensives, antidepressants) * prolonged immobility caused by illness * starvation * physical exhaustion * any condition producing volume depletion (dehydration, diuresis, potassium or sodium depletion) * any condition that results in venous pooling (pregnancy, extensive varicosities of LE) * **Chronic:** may be: * 2' to a specific disease - endocrine disorders (Adrenal insufficiency, diabetes); metabolic disorders (porphyria); diseeases of CNS/PNS (Parkinson, multiple system atrophy, intracranial tumors, cerebral infarcts, Wernick encephalopathy, peripheral neuropathies, cardiovascular autonomic neuropathy 2' to DM) * idiopathic or primary **Clinical Manifestations:** significant risk factor for falls and injury in elderly, increased mortality * dizziness * blurring/loss of vision * syncope caused by insufficient vasomotor compensation & reduction of blood flow through the brain **Treatment:** correct underlying condition (for acute OH or secondary chronic OH); no curative treatment for idiopathic/primary or irreversible secondary OH but management can be adequate with combination of non-drug and drug therapies * increased fluid and salt intake * thigh-high stockings * mineralocorticoids * vasoconstrictors

Answer 161

**Description:** localized dilation/outpouching of a vessel wall or cardiac chamber **Types:** * **True aneurysms:** involve all three layers of the arterial wall; weaking of the vessel wall - most are fusiform and circumferential, saccular aneurysms are spherical in shape * fusiform - bulging in the middle, tapes at both ends * circumferential - all the way around vs saccular - bulging only on one side * **False aneurysm:** an extravascular hematoma that communicates with teh intravascular space (common cause of this type of lesion is a leak b/w vascular graft and natural artery **Causes/Pathophysiology:** aneurysms most commonly occur in thoracic or abdomina aorta (aorta particularly susceptible to due to constant stress on the vessel wall and absence of penestrating vasa vasorum in media layer) * Atherosclerosis - most common cause of arterial aneurysms due to plaque formation eroding vessel wall & contributing to inflammation and release of proteinases that can further weaken the vessel * HTN - contributes by increasing wall stress * Collagen-vascular disorders (eg Marfan syndrome), syphilis, and other infections tht affect arterial walls may also contribute * Cardiac aneurysms most common after MI when intraventricular tension stretches the noncontracting infarcted muscle resulting in a weak and thin layer of necrotic muscle, and fibrous tissue that bulges with each systole **Clinical Manifestations:** depends where aneursym is; those that impair flow to an extremity will cause symptoms of ischemia * _Aortic aneurysms_: often asymptomatic until they rupture, then cause severe pain and hypotension * can be complicated by acute aortic syndromes (aortic dissection, hemorrhage into the vessel wall, or vessel rupture) * Disection of layers of arterial wall occurs when there is a tear in the intima and blood enters walls of the artery; can involve any part of the aorta and disrupt blood flow through arterial branches - S/S: severe pain in neck, jaw, chest, back, or abdo * _Thoracic aortic aneurysms:_ dysphagia (diff. swallowing) and dyspnea (breathlessness) * _Cerebral aneurysms:_ often occur with circle of Willis; S/S of ↑ ICP; S/S of stroke if the aneurysm leaks * _Cardiac aneurysms:_ dysrrhythmias, heart failure, embolism of clots to the brain or other vital organs **Diagnosis:** usually confirmed with ultrasonography, CT, MRI, angiography **Treatment:** * for slow-growing aortic aneurysms: smoking cessation, reduction in BP and blood volume, β-adrenergic blockade * for rapid dilating/enlarged ones: surgical tx and replacement with prosthetic graft * endovascular surgical techniques for aneurysm repair and management of acute aortic rupture * emergent surgical intervention for dissections

Answer 162

* Recall Law of Laplace: wall tension is proportional to vessel radius for a given BP (i.e. ↑ radius = ↑ wall tension) * When an artery wall develops a weak spot and expands as a result, it might seem that the expansion would provide some relief, but in fact the opposite is true * the expansion subjects the weakened wall to even MORE tension (which increases risk of rupture)

Answer 163

**Description:** blood clot that remains attached to the vessel wall **Types of thrombus formation:** * _Arterial thrombi:_ develop when intravascualr conditions promot activation of coagulation OR where there is stasis of blood flow (intimal irritation or roughening such as in surgery, inflammation, trauma, infection, low BP, obstructions causing blood stasis and pooling within vessels ex. aneurysms) * _Valvular thrombi:_ most commonly associated with endocarditis and rheumatic heart disease; altered by calcification or bacterial vegetation **Pathophysiology:** * inflammation of endothelium leads to activation of clotting cascade which causes platelets to adhere readily * widespread arterial thrombus formation can occur in shock (especially sepsis - systemic inflammation activates intrinsic/extrinsic coagulation pathways resulting in microvascular thrombosis through circulation) **Clinical Manifestations/Complications:** thrombus may grow large enought to occlude artery (causing ischemia in tissue supplied by artery); may become dislodged turning into a thromboembolus traveling through vascular system and occluding flow somewhere else **Diagnosis:** Doppler ultrasonography, angiography **Treatment:** meds - heparin, warfarin derivatives, thrombin inhibitors, thrombolytics; balloon-tipped catheter to remove/compress arterial thrombus

Answer 164

**Description:** obstruction of a vessel by an embolus (a bolus of matter circulating in the bloodstream); embolus travels in bloodstream until it reaches a vessel it cannot pass through **Types:** * **Pulmonary emboli:** originate from venous side (most from deep veins in legs) of systemic circulation or in the right heart * **Arterial emboli:** most commonly originate in left heart and associated with thrombi after MI, valvular disease, left HF, endocarditis, and dysrhythmias; most common sites of obstructions are LE (femoral and popliteal arteries), coronary arteries, and cerebral vasculature * **Venous thromboembolism:** dislodged thrombus; source is usually LE; obstructs branches of pulmonry artery * **Air embolism:** air bolus displaces blood in vasculature; source usually room air entering circulation via IV lines; chest trauma allow air from lungs to enter vascular space * **Amniotic fluid embolism:** bolus originate from extensive intra-abdominal pressure attending labor and delivery which forces amniotic fluid into bloodstream of mother; introduces antigens, cells, and protein aggregates that trigger inflammation, coagulation, and immune responses * **Bacterial embolism:** aggregates of bacteria in bloodstream; source is subacute bacterial endocarditis or abscess * **Fat embolism:** fat globules floating in bloodstream associated with trauma to long bones; lungs in particular are affected * **Foreign matter:** small particles or fibers introduced during trauma or through IV or intra-arterial line; coagulation cascade is initiated and thromboemboli form around particles **Complications:** can cause ischemia/infarction in tissues distal to the obstruction, producing organ dysfunction and pain; subsequent necrosis

Answer 165

a dislodged thrombus, an air bubble, an aggregate of amniotic fluid, an aggregate of fat, bacteria or cancer cells, or a foreign substance

Answer 166

**Description:** an inflammatory disease of peripheral arteries; autoimmune condition characterized by formation of thrombi filled with inflammatory and immune cells **Etiology/Risk:** STRONGLY associated with smoking **Pathophysiology:** inflammatory cytokines and toxic oxygen free radicals contribute to accompanying vasospasm; over time, thrombi becoming organized and fibrotic and result in permanent occlusion and obliteraction of parts of small/med- sized arteries in feet (sometimes hands) * body tries to compensate by building collateral vessels (characteristic corkscrew shape due to dilated vasa vasorum in affected artery) but not adequate enough to supply blood extremities **Clinical Manifestations: pain and tenderness in affected part\*** (usually affecting more than one extremity)] * caused by sluggish blood flow * rubor/redness of skin - due to dilated capillaries under skin * cyanosis - from tissue ischemia * thin & shiny skin, and thickened malformed nails (from chronic ischemia) * advanced stages: gangrene need amputation (from vessel obliteration due to profound ischemia) * also associated with CVA, mesenteric disease, and joint pain **Diagnosis:** commonly in age \<45 years, smoking Hx, evidence of peripheral ischemia (with exclusion of other causes of arterial insufficiency) **Treatment: smoking cessation\*** (if they continue to smoke, high chance of disease recurring and gangrene needing amputation) * Other measures to improve circulation to foot/hand * vasodilators to alleviate vasospasms * exercises using gravity to improve blood flow

Answer 167

**Description:** characterized by attacks of vasospasm in the small arteries and arterioles of fingers (& toes but less common) * **Primary Raynaud phenomenon:** common primary vasospastic disorder of unknown origin * **Secondary Raynaud phenomenon:** associated with systemic diseases (collagen vascular disease i.e. scleroderma; vasculitis; malignancy; pulmonary hypertension; chemo; cocaine use; hypothyroidism (myxedema); thoracic outlet syndrome; trauma; serum sickness; or LT exposure to environment conditions like vold temps or vibrating machinery in the workplace) **Cause/Prevalence:** tends to affect young women; characterized by vasospastic attacks triggered by brief exposure to cold, vibration, or emotional stress; potentially genetic predisposition too **Pathophysiology:** blood vessels have endothelial dysfunction with imbalance of endotheliuem-derived vasodilators (i.e. NO) and vasoconstrictors (endothelin-1); platelet activation and autoantibodies may also be involved **Clinical Manifestations:** * changes in skin colour and sensation caused by ischemia * vasospasm with varying frequency and severity - causes pallor, numbness, sensation of coldness in fingers/toes * bilateral manifestation, usually starts at tips of digits & progress proximally * cyanosis (from sluggish blood flow 2' to ischemia) * rubor, throbbing pain and paresthesia as blood flow returns (and then skin colour returns to normal) * frequent prolonged attacks cause skin of fingertips to thicken and brittle nails * ulcers and gangrene (severe) **Diagnosis:** S/S and nailfold capillaroscopy; hx of associated diseases **Treatment:** remove stimulus or treating primary disease process * starts with removing stimulus, smoking cessation (to eliminate vasoconstriction caused by nicotine) * if attacks prolong, use of vasodilators (calcium chanel blockers, NO agonists, alpha-blockers, prostaglandin analogs, endothelin antagonists) * sympathectomy (severe) but may not be effective * amputation (if ulceration and gangrene)

Answer 168

**Arteriosclerosis:** condition characterized by thickening and hardening of vessel wall **Atherosclerosis:** form of areriosclerosis caused by accumulation of lipid-laden macrophages within arterial wall, leading to formation of lesion AKA plaque * not a single disease entity but a pathologic process that leads to a variety of other ischemic syndromes * LEADING cause of CAD and CVD

Answer 169

**Description:** form of arteriosclerosis that is caused by the accumulation of lipid-laden macrophages within the arterial wall leading to plaque formation **Risk Factors:** smoking, HTN, diabetes, increased LDL levels, decreased HDL, autoimmunity; nontraditional risk factors: increased serum markers for inflammation and thromvosis (high-sensitvity C-reactive protein [hs-CRP], troponin I, adipokines, infection, and air pollution) **Pathophysiology:** ^ factors cause endothelial injury to artery walls = inflammation * inflamed endothelial cells can't make normal amounts of antithrombis and vasodilating cytokines * cells then express adhesion molecules that bind macrophages and other inflammatory and immune cells (macrophages activated by DAMPs released from injured cells and release inflammatory cytokines that cause further vessel injury) * inflammatory process also generates free radicals that oxidize LDL that has accumualted in vessel intima = additional adhesion molecule expression and recruitment of more monocytes (and thus macrophages) * macrophages penetrate intima and engulf oxidized LDL (now are lipid-laden and called **foam cells**, and if ++ amounts accumulated, they form a lesion called **fatty streak**) * fatty streaks produce more toxic free radicals, recuit T cells leading to autoimmunity, and secrete additional inflammatory mediators resulting in progressive damage to vessel wall * macrophages also release growth factors that stimulate smooth muscle cell proliferation (causing collagen production that then moves over to fatty streak to form a **fibrous plaque)** - may calcify, protrude into vessel lumen and obstruct blood flow to distal tissues and cause sx (angina, intermittent claudication) * plaques may be unstable and rupture and potential bleeding within lesion (aka **complicated plaques**) ⇒ exposes underlying tissue ⇒ initiation of thrombus formation which runs the risk of occluding affected vessel ⇒ ischemia and infarction **Clinical Manifestations:** S/S resulting from inadequate tissue perfusion due to vessel obstruction (depends on where the plaque build up occurs) * partial obstruction: transient ischemic events (often with exercise, stress( * can progress to tissue infarction * obstruction of peripheral arteries: ++pain and disability * CAD * stroke **Diagnosis:** hx taking (risk factors, S/S); physical exam showing arterial bruits (vascular murmurs signifying turbulent blood flow) and evidence of decreased blood flow to tissues; lab data measure lipid levels, blood glucose, hx-CRP; various diagnostic tests (X-rays, ECG, CT, MRI, etc.) to identify affected vessels **Treatment:** prevention via ASA or other antithrombotic agents * If immediate Ix is not needed: reduction of risk factors to prevent plaque progression (exercise, smoking cessation, controlling HTN and diabetes to reduce LDL, diet, medications) * If blood flow is obstructed, primary goal is restoring adequate blood flow (Ix are specific to the diseased area)

Answer 170

**Description:** refers to atherosclerotic disease of arteries that perfuse limbs, especially LE * can be gradual or acute * in most, gradual obstruction of blood flow to legs caused by atheroscleoris in iliofemoral vessels results in pain with ambulation (**intermittent claudication**) **-** pain, discomfort, numbness, or tiredness * acute: if thrombus forms over atherosclerotic lesion causing complete obstruction of blood flow - severe pain, loss of pulse, skin colour changes in affected extremity **Risk factors:** same as those for atherosclerosis, but especially prevalent in elderly with diabetes; strong link with smoking **Clinical Manifestations:** as mentioned above in gradual vs acute types, but know that although PAD has increased mortality, over 2/3 of ppl with it are asymptomatic even in severe cases **Diagnosis:** hx and physical exam (finding bruits), ankle-brachial index (finding BP difference measured at snkle vs arm), measuring blood flow via noninvasive Doppler **Treatment:** reduction of risk factors (smoking cessation, tx of diabetes, HTN, DLD); antiplatelet therapy * symptomatic PAD should be managed with vasodilators x antiplatelet/ antithrombotic medications and cholesterol-lowering medications * aerobic exercise * emergent percutaneous or surgical revascularization for acute/uncontrolled symptoms

Answer 171

Coronary artery disease (CAD) **\*note**: Coronary artery disease, myocardial ischemia, and myocardial infarction form a pathophysiologic continuum that impairs the pumping ability of the heart by depriving the heart muscle of blood-borne oxygen and nutrients.

Answer 172

* CAD can diminish myocardial bood supply until deprivation impairs myocardial metabolism enough to cause ischemia (cells remain alive but not functioning normally) * Persistent ischemia or the complete occlusion of a coronary artery causes the **acute coronary syndromes** including infarction, or irreversible myocardial damage * Infarction constitutes **heart attacks**

Answer 173

**Conventional x non-modifiable:** advanced age, male gender or women after menopause, family hx (genetics/shared environment exposures) * aging and menopause are associated with increased exposure to risk factors and poor endothelial healing **Modifiable:** DLD, HTN, cigarette smoking, diabetes and insulin resistance, obesity, sedentary lifestyle, atherogenic diet (Western-type diets - high in saturated fats and cholesterol) **Non-traditional risk factors:** increasd serum markers for inflammation and thrombosis (troponin I, adipokines, infection, and air pollution), CKD, hyperhomocysteinemia, medications, microbiome

Answer 174

* Lipid metabolism: chylomicrons are little particles that dietary fat is packaged into, transported in the body, and then the remainders (cholesterol) are taking up by the liver to produce very low-density lipoproteins (VLDLs), LDLs, and HDLs * **Dyslipidemia:** abnormal concentrations of serum lipoproteins (due to genetics x dietary factors) * LDL is responsible for delivery of cholesterol to tissues and increased [LDL] is a STRONG indicator of coronary risk * high levels of LDL contribute to its migration into vessel wall, oxidation, and phagocytosis by macrophages (process in plaque formation) * LDL also plays a role in endothelial injury, inflammation, and immune responses that have been identified as being important in atherogenesis * elevated levels of serum VLDLs (triglycerides) and increased lipoprotein(a) levels also increase CV risk * low HDL levels also strong indicator or coronary risk (HDL is repsonsible for returning excess cholesterol in tissues to liver for processing/elimination; also involved in endothelial repair and decreased thrombosis)

Answer 175

* HTN increases risk of atherosclerotic CV disease by two- to three-fold * contributes to endothelial injury (thus atherogenesis) * can also cause myocardial hypertrophy increasing oxygen demands

Answer 176

* direct and passive (environmental) smoking increases risk of CAD * smoking has direct effect on endothelial cells and generation of oxygen free radical contributing to atherogenesis * nicotine stimulates release of catecholamins (epinephrine and norepinephrine) increasing HR and peripheral vascular constriction (∴ ↑BP, cardiac workload, and oxygen demand) * also associated with increased LDL levels, decreased HDL levels

Answer 177

* Insulin resistance and diabetes have multiple effects on CV system including damage to endothelium, thickening of vessel wall, increased inflammation, incresed thrombosis, glycation of vascular proteins, and decreased production of endothelial-derived vasodilators (NO) * DM also associated with DLD

Answer 178

* **metabolic syndrome:** combo of obesity, DLD, HTN, and insuling resistance - associated with high risk of CAD events * abdominal obesity - strongest link with increased CAD risk; related to inflammation insulin resistance, decreased HDL level, increased BP, and fewer changes in adipokines (leptin and adiponectin) * Sedentary lifestyle - increases risk of obesity and CAD (gastric bypass may reduce risk factors)

Answer 179

* Diet high in salts, fats, trans-fats, and carbs = higher risk of CAD * most effective diet mods: **mediterranean diet** * ****high intake of olive oil, fruits, nuts, veggies, cereals * mod intake of fish and poultry; wine with meals * low intake of dairy products, red meat, processed meats, and sweets

Answer 180

* mostly synthesized in the liver and used as an indirect measure of atherosclerotic plaque-related inflammation * elevated serum levels of hs-CRP strongly correlated with increased risk for coronary events (**note:** it is a nonspecific measure of inflammation though, so may indicate prescence of other inflammatory conditions) * used as an aid to determine appropriate pharm Ix for those with other risk factors for coronary disease

Answer 181

* hs-CRP * protein C * plasminogen activator inhibitor * eyrthrocyte sedimentation rate (ESR) * von Willebrand factor * IL-6 * IL-18 * TNF * fibrinogen * CD 40 ligand

Answer 182

* serum protein whose measurement is used as a sensitive and specific Dx test to help identify myocardial injury during ACS * used to assess risk (in those c/o hx of CAD) for future CHD events, mortality, and heart failure

Answer 183

* group of hormones released from adipose cells (leptin, adiponectin) * obesity causes ↑ leptin levels (and involved in HTN and diabetes) & ↓ adiponectin (which typically functions to protect vascular endothelium and is anti-inflammatory) * ↓ adiponectin and ↑ leptin are associaed with inflammation, endothelial injury, and thrombosis * weight loss, exercise, and health diet improve adipokine levels

Answer 184

* infection with various microorganisms (*Chlamydia pneumoniae, Helicobacter pylori,* and cytomegalovirus) have been linked to increased CAD risk * periodontal disease also increases CAD risk * unknown clear cause but potentially due to system infection increasing inflammation of vessels and thus contributing to vascular disease

Answer 185

* exposure to air pollution (esp. roadway exposures) STRONGLY correlated with coronary risk * toxins in pollution contribute to macrophage activation, LDL oxidation, thrombosis and inflammation of vessel walls * Exposure to even low levels of ionizing radiation also has been linked to increased risk for CAD

Answer 186

* a decline in GFR is associated with an increasing risk for CAD * CKD is associated with dyslipidemia, endothelial injury, and vascular calcification, which contribute to atherogenesis

Answer 187

* meds may contribute to CAD through their effect on lipid metabolism, clotting, or other effects on vascular function and tone * NSAIDs linked to increase in CAD-related ischemic events that can occur within weeks of beginning their use * Likely mechanisms: increases in toxic oxygen radicals, vasoconstrictors, and thrombosis

Answer 188

* Changes in the microbiome have been found to have significant effects on the development of traditional risk factors for cardiovascular disease, such as diabetes and obesity

Answer 189

**Description:** local, temporary deprivation of of coronary blood supply **Pathophysiology:** Myocardial ischemia develops if the flow or oxygen content of coronary blood is insufficient to meet the metabolic demands of myocardial cells * various causes, but most common is atherosclerotic plaques in the coronary circulation; other causes: coronary spasm, hypotension, dysrhythmias, decreased oxygen-carrying capacity of the blood (anemia, hypoxemia) * common causes of increased myocardial demand: tachycardia, exercise, HTN (hypertrophy), and valvular disease * plaque can increase in size and partially occlude the vessel lumin thus causing ischemia (especially during exercise) * plaques can be "unstable" and ulcerate/rupture leading to exposed tissue and thrombus formation ⇒ acute ischemia that can turn into infarction * myocardial cells become ischemic within 10 seconds of coronary occlusion (deprives glucose source needed for aerobic metabolism so anaerobic metabolism kicks is and lactic acid accumulates) * After several mins, heart cells lose ability to contract and CO decreases * Cardiac cells remain viable for ~20 min; if blood flow is not restored, MI occurs **Clinical Manifestations:** several presentations (covered in upcoming flashcards) * _Stable angina:_ chronic coronary obstruction that results in recurrent predictable chest pain * _Prinzmetal angina:_ abnormal vasospasm of coronary vessels reuslting in unpredictable chest pain * _Silent ischemia_: myocardial ischemia that does not cause detectable sx **Diagnosis:** if reversible myocardial ischemia, physical exams will be normal between events but DURING ischemia, will have ↑ HR, extra heart sounds (gallops/murmurs), pulmonary congestion indicated left ventricular function * presence of xanthelasmas (small fat deposits) around eyelids/arcus senilis of eyes (yellow lipid rings around corner) - suggests severe DLD and possible atherosclerosis * presence of peripheral/carotid artery bruits * ECG * transient ST depression and T wave inversion - signs of ischemia involving only inner wall of myocardium * ST elevation indicative of full myocardial wall ischemia (transmural ischemia) * Stress radionucleotide imagig - to detect ischemic changes in asymptomatic individuals with multiple risk factors for coronary disease * Single photon emission computerized tomography (SPECT)\* - identifies ischemia and estimated coronary risk * Stress echocardiography * Various CT scans, MRI, ultrasound **Treatment:** increase coronary blood flow and reduce myocardial oxygen consumption (for myocardial ischemia and stable angiong) - diet, exercise, risk reduction, statins meds * improve coronary blood flow via reversing vasoconstriction, reducing plaque growth and rupture, preventing clotting * myocardial oxygen demand is reduced via manipulation of BP, HR, contractility and LV volume * drugs to increase coronary flow and decrease myocardial demand - nitrates, beta-blockers, calcium channel blockers * **Percutaneous Coronary Intervention (PCI)** - procedure where stenotic cronary vessels are dilated with a catheter * Meds: antithrombotics (ASA, Plavix, glycoprotein IIb/IIIa receptor antagonists) * CABG - coronary artery bypass graft (for severe CAD) which uses saphenous vein from lower leg (OR a modified procedure known as MIDCAB that has less surgical morbidity and more rapid recovery)

Answer 190

1) stable angina pectoris 2) Prinzmetal angina 3) silent ischemia/mental stress-induced ischemia

Answer 191

**Description:** chest pain caused by myocardial ischemia **Cause:** gradual luminal narrowing and hardening of the arterial walls c/ associated inflammation, endothelial cell dysfunction, and decrease in endogenous vasodilators **Prevalence:** changes in vessel wall more prevalent in obesity, diabetes, DLD **Pathophysiology:** affected vessels cannot dilate in response to increased myocardial demand (exercise, stress); blood flow restored with rest and no necrosis occurs **Clinical Manifestations:** transient substernal chest discomfort, varies from heaviness/pressure to moderately severe pain (pain caused by lactic acid buildup or abnormal stretching of ischemic myocardium that irritates myocardial nerve fibers * clenching fist over L sternal border * discomfort mistaken for indigestion * discomfort radiating to neck, lower jaw, left arm, left shoulder, occasionally to the back and down the R arm * pallor, diaphoresis, dyspnea * pain relieved with rest and nitrates (like nitro) **Treatment:** recommendation sof apropriate diet, exercise, risk reduction; Ranolazine (Na+ channel inhibitor) which improves exercise tolerance, less angina sx, and reduce need for nitrates

Answer 192

* women with myocardial ischemia typically have no sx, or atypical sx (atypical chest pain, palpitations, anxiety, weakness, fatigue, sense of unease * ~half of women with stable angina DO NOT have obstructure CAD but rather **microvascular angina (MVA)** * small intramyocardial arterioles constrict causing ischemic pain that is less predictable than typical CAD * Potential contributing factors: endothelial dysfunction, decreased endogenous vasodilators, inflammation, changes in adipokines, and platelet activation * **Treatment:** management via smoking cessation, exercise, diabetes management, use of non-nitrate vasodilators (nitrates cause less dilation than in those without MVA) * other approaches: spinal cord stimulation; adenosine receptor blockade

Answer 193

**Description:** aka variant angina; chest pain attributable to transient ischemia of myocardium that occurs unpredictably and often at rest **Causes/Pathophysiology:** may result from decreased vagal activity, hyperactivity of SNS, or decreased NO activity * Other causes: altered calcium channel function in arterial smoothe muscle or impaired production or release of inflammatory mediators (serotonin, histamine, endothelin, thromboxane) **Clinical Manifestations:** pain caused by vasospasm of one or more major coronary arteries with or without associated atherosclerosis * pain often occurs at night during REM, may have cyclic pattern of occurrence * elevated levels of serum markers of inflammation (CRP, IL-6) **Treatment:** calcium channel blockers or long acting nitrates (vasodilator therapy); condition is usually benign but can occasionally cause serious dysrhythmias especially if treatment is withdrawn

Answer 194

**Description:** asymptomatic ischemia (or those with complaints of fatigue, dyspnea, feeling unease **Cause:** potentially due to presence of global/regional abnormality in LV sympathetic afferent innvervation; * most common cause of autonomic dysfunction: DM * other causes: surgical denervation during CABG or cardiac transplantation * following ischemic local nerve injury by MI * can occur during mental stress (due to increased inflamamtory cytokines and hypercoagulable state that may contribute to acute ischemic events) **Diagnosis:** detected by stress radionucleotide imaging

Answer 195

Plaque progression leading to sudden coronary obstruction caused by thrombus formation over a ruptured atherosclerotic plaque * **Unstable angina**: reversible form of ACS, warning sign of impending infarction * **Myocardial infarction (MI):** results from prolonged ischemia causing irreversible damage to the heart * **non-ST elevation MI (non-STEMI)** * **ST evelation MI (STEMI)** * sudden cardiac death canc occur as a result of any of the ACSs

Answer 196

* these plaques are rich in oxidized LDL and a thin fibrous cap * ulceration/rupture occurs because of effects of shear forces, inflammation with release of multiple inflammatory mediator, secretion of macrophage-derived degradative enzymes, and apoptosis of cells athe edges of the lesions * exposure of plaque substance activates clotting cascade and platelet activation * vessel obstruction is further exacerbated by the release of vasoconstrictors, such as thromboxane A₂ and endothelin * thrombus make break apart before permanent myocyte damage has occured (\<20 mins) - unstable angina OR if prolonged, then MI

Answer 197

**Description:** form of ACS resulting from _reversible myocardial ischemia_; signals that atherosclerotic plaque has become complicated and may soon lead to infarction * occurs when a small opening/superficial erosion of plaque leads to transient episodes of thrombotic vessel occlusion and vasoconstriction at the site of plaque damage * thrombus can easily change and occludes vessel for no more than 10-20 minutes, with return of perfusion before significant myocardial necrosis occurs **Clinical Manifestations:** presents as new-onset angina, angina that is occuring at rest, or angina that is increasing in severity or frequency * dyspnea, diaphoresis, anxiety as angina worsens **Diagnosis:** physical exam (showing ischemic myocardial dysfunction such as pulmonary congestion) * ECG shows ST depression and T wave inversion during pain; resolves as pain is relieved **Treament:** same guidelines as non-STEMI → immediate hospitalization with O₂ administration, ASA, nitrates, morphine (for pain) * potential indications for antithrombotic therapy (Plavix, glycoprotein IIb/IIIa platelet receptor antagonists - inhibits platelet aggregation) * Beta-blockers, ACE inhibitors - as necessary * anticoagulants (low MW heparin) or direct thrombin inhibitors - as necessary * Rapid PCI (balloon stent - as necessary)

Answer 198

**1) Rest angina** - angina occurring at rest and prolonged, \>20 min **2) New onset angina** - new onset anging of at least CCC (Canadian CV Society) Class III severity **3) Increasing angina -** previously diagnosed angina that has become distinctly more frequent, longer un duration, or lower in threshold

Answer 199

**Description:** the result of interrupted coronary blood flow for an extended period off time leading to myocyte necrosis; same plaque progression, disruption and subsequent clot formation as unstable angina BUT thrombus is less labile and occludes vessel for prolonged period * two major types: BUT clinically categorized as non-STEMI or STEMI * **subendocardial infarction/non-STEMI:** if thrombus disintegrates before complete distal tissue necrosis has occurred, infarction will involve only myocardium directly beneath endocardium - presents as ST depression with T wave inversion without Q waves * recurrent clot formation is likely and may become lodged permanently leading to a transmural infarction * **transmural infarction/STEMI**: thrombus lodged causing infarction to extend through myocardium (from endocardium to epicardium); usually ST elevation

Answer 200

* after 8-10 seconds of decreased blood flow, affected myocardium becomes cyanotic and cool * myocardial oxygen reserves are used quickly; glycogen stores decrease as anaerobic metabolism begins * lactic acid and H+ builds up from ^ which further compromises myocardium (they have poor buffering abilities) → acidosis may increase susceptibility to damaging effects of lysosomal enzymes and suppress impulse conduction and contractile function (∴ heart failure) * electrolyte disturbances (loss of K+, Ca++, Mg++ from cells) ↓ pumping ability * ischemia causes release of catecholamines leading to imbalances of SNS/PNS function , dysrhythmias, and HF * Catecholamines mediate release of glycogen, glucose, and stored fat from body cells which can harm cell membranes * Angiotensin II is released and contributes to development of MI (peripheral vasoconstriction & fluid retention = ↑ workload; a growth factor that causes myocardium remodeling; ↑ catecholamine release causing coronary artery spasm) * Cardiac cells can withstand ischemic conditions for ~20 minutes before irreversible hypoxic injury causes apoptosis and tissue necrosis

Answer 201

* gross tissue changes at area of infarction may not become apparent for several hours although immediate onset of ECG changes * **Myocardial stunning:** temporary loss of contractile function persisting for hours to days after perfusion has been restored * caused by alterations in electrolyte pumps and calcium homeostasis and by release of toxic oxygen free radicals * contributes to HF, shock, dysrhythmias * **Hibernating myocardium:** describes tissue that is persistently ischemic and undergoes metabolic adaptation to prolong myocyte survival until perfusion can be restored (via PCI or surgery) * **Myocardial remodeling:** myocyte hypertrophy and loss of contractile function in areas of the heart distant from infarction site (mediated by Ang II, aldosterone, catecholamines, adenosine, inflammatory cytokines) * can be limited with rapid restoration of blood flow; RAAS blockers and beta-blockers after MI * Functional impairment depends on lesion size and infarction site, can include: * 1) decreased cardiac contracility with abnormal wall motion * 2) altered LV compliance * 3) decreased SV * 4) decreased EF (due to abnormal ventricular function) * 5) increased LV end-diastolic pressure (↑VEDV) * 6) SA node malfunction

Answer 202

PRocess involves release of toxic oxygen free radicals, calcium flux, and pH changes tha cause sustained opening of mitochondrial permeability transition pores (mPTPs) and contirbute to resultant cellular death

Answer 203

inflammatory; wound repair * damaged cells undergo degradation, fibroblasts proliferate, scar tissue made * within 24 h, leukocytes infiltrate necrotic area and neutrophils degrade tissue * collagen matrix is deposited (initially weak, mushy, vulnerable to re-injury ~ 10-14 days post infarction) but can be easily stressed because people at this period of time start to feel like increasing activities * After 6 weeks, necrotic area is completely replaced by scar tissue (strong but cannot contract/relax like healthy myocardial tissue)

Answer 204

* sudden, severe chest pain (similar to angina pectoris but more severe and prolonged) * heavy, crushing "truck sitting on chest" * Commonly radiates to neck, jaw, back, shoulder, L arm * Elderly/those with diabetes, may experience no pain (silent infarction) * indigestion that doesn't go away * N/V may occur - due to reflex stimulation of vomiting centers by pain fibers * vasovagal reflexes from area of infarcted myocardium may affect GI tract

Answer 205

On physical examination: 1. SNS is reflexively activated to compensate, resulting in temp increase in HR and BP 2. abnormal extra heart sounds reflecting LV dysfunction 3. pulmonary findings of congestion including dullness to percussion and inspiratory crackles at lung bases (can occur if person develops heart failure) 4. peripheral vasoconstriction may cause skin to become cool and clammy

Answer 206

1) ischemia 2) LV dysfunction 3) electrical instability

Answer 207

* Disturbances of cardiac rhythm that affect 90% of persons with cardiac infarction * Caused by ischemia, hypoxia, ANS imbalances, lactic acidosis, electrolyte abnormalities, alterations of impulse conduction pathways or conduction abnormalities, drug toxicity, or hemodynamic abnormalities * sudden onset of tachycardia or bradycardia, palpitations, syncope, shock, or sudden death

Answer 208

* Characterized by pulmonary congestion, reduced myocardial contractility, and abnormal heart wall motion * Cardiogenic shock can develop

Answer 209

Inflammation of the pericardium associated with anterior chest pain that worsens with respiratory effort and pericardial friction rub; occurs 2 to 3 days after infarction

Answer 210

* Delayed form of pericarditis that occurs 1 week to several months after acute MI and thought to be immunologic response to necrotic myocardium * marked by pain, fever, friction rub, pleural effusion, and arthralgias

Answer 211

Occurs if blood flow to brain is impaired 2' to MI

Answer 212

* caused by necrosis of tissue in/around papillary muscles * acute onset of severe valvular regurgitation * Predisposing factors include thinning of wall, poor collateral flow, shearing effect of muscular contraction against stiffened necrotic area, marked necrosis at terminal end of blood supply, and aging of myocardium with laceration of myocardial microstructure

Answer 213

Occur if thromboemboli detach from clots that form in cardiac chambers or on cardiac valves

Answer 214

Can be caused by aneurysm formation when pressure becomes too great

Answer 215

* Late (month to years) complication of MI that can contribute to heart failure and thromboemboli * Aneurysm formation resulting from high chamber pressures and volume pushing against weakened ventricular wall

Answer 216

* Occur in those structures that separate heart chambers and lead to septal rupture * Associated with audible, harsh cardiac murmurs; increased left ventricular end-diastolic pressure; and decreased systemic blood pressure

Answer 217

May disseminate from debris and clots that collect inside dilated aneurysmal sacs or from infarcted endocardium; can affect any system but especially targets cerebrovascular system with transient ischemic attacks and stroke

Answer 218

* Usually from deep venous thrombi of legs * acute onset of dyspnea and hypoxemia * Reduced incidence associated with early mobilization and prophylactic anticoagulation therapy

Answer 219

* frequently caused by dysrhythmias, particularly v-fib * Risk of death increased by age more than 65 years, previous angina pectoris, hypotension or cardiogenic shock, acute systolic hypertension at time of admission, diabetes mellitus, dysrhythmias, and previous MI

Answer 220

* history taking * physical exam * 12-lead ECG to identify affected area through changes in ST segments and T waves * characteristic Q wave often develops some hours later in STEMI * **serial cardiac troponin elevations (troponin I and troponin T)** * **cTn1 -** most specific indicators of MI (levels should be measured on ED admission - elevation should be detectable 2-4 hrs after Sx onset) and then subsequent measurements needed * can also help estimate infarct size and thus likelihood of complications * additional lab data make show leukocytosis (elevated leukocyte levels) and elevated CRP (both indicate inflammation) * elevated blood glucose level

Answer 221

Acute MI * hospital admission * aspirin immediately (ticlopidine if allergic to aspirin) * Pain relief - sublingual nitroglycerin and morphine sulfate * continuous moitoring of cardiac rhythms and enzymatic changes (first 24h after sx onset is high risk for sudden death) * emergent PCI and antithrombotics * insulin - for hyperglycemia * once stabilized: further management via ACE inhibitors, beta-blockers and statins * if in shock, fluid resus, ionotropic drugs, and possible surgical procedures Non-STEMI: same treatment as unstable angina (antithrombotics, anticoagulants or PCI, or both) * best rest and then gradual return to ADLs to reduce myocardial oxygen demands of the compromised heart * DVT prophylaxis if not taking heparin/thrombolytics * stool softeners to decrease need for straining (and possible cardiac overload) * Education on diet, caffeine intake, smoking, exercise, risk reduction

Answer 222

* localized manifestation of another disorder (infection, trauma/surgery, cancer, metabolic, immunologic, or vascular) * pericardial disease may consist of: * **acute pericarditis** * **percardial effusion** * **constrictive pericarditis**

Answer 223

**Description:** acute inflammation of the pericardium; the most common CV complication of HIV infection **Etiology:** most often idiopathic or caused by viral infection by coxsackie, influenze, hepatitis, measles, mumps, or varicella viruses * other causes: MI, trauma, cancer, surgery, uremia, bacterial infection (esp. TB), connective tissue disease (esp. SLE and RA), or radiation therapy **Pathophysiology:** percardial membranes become inflamed and roughened, and a pericardial effusion may develop that can be serous, purulent, or fibrinous * possible sequelae - recurrent pericarditis, percardial constriction, cardiac tamponade **Clinical Manifestations:** Sx may folllow several days of fever and usually begin with sudden onset of severe retrosternal chest pain that worsens with respiratory movements and when assuming a recumbent position (lying down) * pain radiating to back due to irritation of phrenic nerve which innervates trapezius muscles * dysphagia, restlessness, irritability, anxiety, weakness, malaise **Diagnosis:** * low grade fever (\<38 C) and sinus tach; * friction rub (scratchy, grating sound - caused by roughened pericardial membranes rubbing against each other; may be intermittent) may be heard at cardiac apex and left sternal border * hypotension or presence of pulsus paradoxus (↓ in SBP \> 10mmHg with inspiration) - suggestive of cardiac tamponade * ECG: PR segment depression; diffuse ST segment elevation without Q waves (can be abnormal for days/weeks) * Ultrasound, CT, MRI * Requires a least two of the following criteria: * 1) chest pain characteristics of pericarditis * 2) pericardial rub * 3) characteristic ECG changes * 4) new or worsening pericardial effusion **Treament: for uncomplicated acue pericarditis -** symptom relief (administration of anti-inflammatories, ex. salicylates and NSAIDs, colchicine) * for complicated pericarditis (development of idiopathic recurrent pericarditis) - find out underlying cause if possible; potential need for excess fluid aspiration if percardial effusion develops

Answer 224

**Description:** accumulation of fluid in pericardial cavity; can occur in all forms of pericarditis **Etiology:** 20% (most) are idiopathic; other potential causes: neoplasms, infection * fluid can be transudate (filtered plasma) - from LHF, overhydraiton or hypoproteinemia * fluid that is exudate (more common) - indicative of pericardial inflammation seen with pericarditis, heart surgery, chemo drugs, infections, autoimmune disorders * fluid with serum x blood - underlying cause is TB, neoplasms, uremia, or radiation; or idiopathic * effusions with frank blood - aneurysms, trauma, coagulation defects **Pathophysiology:** effusions can develop gradually in which percardium will stretch to accommodate without compressing the heart * if fluid accumulates rapidly (50-100mL) it may compress heart (**tamponade**) * pressure exerted by pericardial fluid will eventually = diastolic presure within heart chambers which will interfere with right atrial filling during diastole (leads to increased venous pressure, S/S of right HF - JVD, edema, hepatomegaly) * ↓ atrial filling leads to ↓ventricular filling, ↓ SV, reduced CO **Clinical Manifestations:** * **Pulsus paradoxus:** arterial BP during expiration \> arterial BP during inspiration by \>10 mmHg (due to impairment of diastolic filling of LV + reduction of blood volume within all four cardiac chambers) * distant/muffled heart sounds * poorly palpable apical pulse * dyspnea on exertion * dull chest pain **Diagnosis:** X-ray will show "water-bottle configuration" of heart; ECHO can etect effusion; CT scans **Treatment:** pericardiocentesis (aspiration of excessive pericardial fluid) ; tx of underlying condition; persistent pain: analgesics, anti-inflammatory meds, steroids; creating a percardial window via srugery to prevent tamponade

Answer 225

**Description:** aka chronic pericarditis; characterized by fibrous scarring with occasional calcification of the pericardium causing the visceral and parietal pericardial layers to adhere, obliterating the pericardial cavity (heart is encased in a rigid shell and is compressed leading to eventual reduction in CO) - different than tamponade because constrictive pericarditis always develops gradually * synonymous with TB in the past (as TB is an important cause in immunocompromised ppl) **Etiology:** more commonly idiopathic or associated with viral infection, radiation exposure, collagen vascular disorders, sarcoidosis, neoplasm, uremia, or cardiac surgery **Clinical Manifestations:** exercise intolerance, dyspnea on exertion, fatigue, and anorexia * edema, JVD, hepatic congestion, systemic hypotension * restrictive ventricular filling causing pericardial knock (early diastolic sound) **Diagnosis:** ECG - nonspecific ST and T wave abnormalities, a-fib * X-ray films show prominent pulmonary vessels and calcification of pericardium * CT, MRI, transesophageal echo to detect pericardial thickening and constriction * potentially pericardial biopsy **Treatment:** initial tx: dietary restriction of sodium intake; administration of diuretics to improve CO; anti-inflammatory drugs and tx of underlying disorder * if ^ unsuccessful, then surgical excision of restrictive pericardium (pericardial decortication)

Answer 226

* diverse group of diseases that primarily affect myocardium * can be 2' to infectious disease, ischemia, toxin exposure, systemic connective tissue disease, infiltrative and proliferative disorders, or nutritional deficiencies * many are idiopathic * categorized as: * **dilated (previously, congestive)** * **hypertrophic** * **restrictive**

Answer 227

* characterized by impaired systolic function leading to increases in intracardiac volume, ventricular dilation, and heart failure with reduced EF * heart has a globular shape and largest circumference of the LV is not at the base but midway between apex and base * result of ischemic heart disease, valvular disease, diabetes, renal failure, alcohol or drug toxicity, peripartum complications, or infection * strong genetic basis for dilated cardiomyopathy; can be associated with inherited disorders (ex. muscular dystrophy) * **Sx:** dyspnea, fatigue, pedal edema * **Findings:** displaced apical pulse, S₃ gallop heart sound, peripheral edema, JVD, pulmonary congestion * **Diagnosis:** Chest x-ray and echo * **Treatment:** reducing blood volume, increased contractility, reversing underlying disorder; heart transplant for severe cases

Answer 228

* refers to two major categories of thickening of myocardium * **1) hypertrophic obstructive cardiomyopathy**/**asymmetrical septal hypertrophy:** most commonly inherited cardiac disorder and characterized by thickening of septal wall which may cause outflow obstruction to the L ventricle outflow tract; * obstruction can occur with ↑ HR and ↓ intravascular volume * this type is ++risk factor for ventricular dysrhythmias and sudden death * **2) hypertensive/valvular hypetrophic cardiomyopathy:** most common; occur due to increased resistance to ventricular ejection, which is commonly seen those with HTN or valvular stenosis * hypertrophy of myocytes is an attempt to compensate for increased myocardial workload * LT dysfunction of myocytes develop over time (diastolic dysfunction happens first, then systolic dysfunciton * may be asymptomatic or may complain of angina, syncope, dyspnea on exertion and palpitations * exam shows extra heart sounds and murmurs * wall in LV is greatly thickened (look at pic)

Answer 229

* characterized by restrictive filling and increased diastolic pressure of either or both ventricles with normal or near normal systolic function and wall thickness * **Cause:** may be idiopathy or as a cardiac manifestation of systemic diseases (amyloidosis, scleroderma, sarcoidosis, lymphoma, and hemochromatosis) * **Patho:** myocardium becomes rigid and noncompliant, impeding ventricular filling and raising filling pressures during diastole * **S/S:** most common clinical manifestation of restrictive cardiomyopathy is right heart failure with systemic venous congestion * **Dx:** evaluation for underlying cause * **Treatment:** tx underlying cause; death occurs 2' to heart failure or dysrrhythmias

Answer 230

* caused by damge to endocardium (innermost lining of heart wall) * can be congenital or acquired * acquire forms result from inflammatory, ischemic, traumatic, degenerative, or infectious alterations of valvular structure and function (one of the most common causes of acquired - rheumatic heart disease) * structural alterations of heart valves are caused by remodeling changes in valvular ECM and lead to stenosis/incompetence

Answer 231

* valve orifice is constricted/narrowed so blood canont flow fowrad and chamber proximal to diseased valve has increased workload * pressure rises in chamber to overcome resistance to flow meaning that greater exertion by myocardium is needed = myocardial hypetrophy * any heart valve can be affected but MOST common are mitral and aortic valves

Answer 232

* aka **valvular insufficiency/incompetence** * characterized by cusps failing to shut completely which permits blood flow to continue even when valve is presumably closed * **Patho:** During systole or diastole, some blood leaks back into the chamber proximal to the diseased valve, incresing the volume of blood the heart must pump and increases the workload of both the atrium and the ventricle * increased volume leads to chamber dilation, increased workload thus hypertrophy (compensatory but both can lead to cardiac dysfunction over time) * Eventually, myocardial contractility diminishes, EF drops, and diastolic pressure increases, and the ventricles fail from being overworked * **Diagnosis:** transthoracic echo (TTE) used to assess severity of valvular obstruction or regurgitation before onset of Sx * CT, MRI * valvular lesion staging: 1) a risk, 2) progressive, 3) aymptomatic severe 4) symptomatic severe * **Treatment:** careful medical management, valvular repair, or valve replacement followed by LT anticoagulation therapy and prophylaxis for endocarditis

Answer 233

**Description:** most common valvular abnormality **Prevalence:** affects nearly 2% of those 65+; associated with many risk factors for CAD (HTN, smoking, DLD) **Cause:** three common causes - 1) congenital bicuspid valve, 2) degeneration with aging, and 3) inflammatory damage caused by rheumatic heart diseae * associated with aging due to chronic inflammation, lipoprotein deposition in tissue, and leaflet calcification **Pathophysiology:** orifice of valve narrows causing resistance of blood flow from LV to aorta * Outflow obstruction increases pressure within the LV as it tries to eject blood through the narrowed opening = LV hypertrophy to compensate increase workload = ↑ oxygen demand * can lead to ischemia (and angina) if coronary arteries cannot meet oxygen demand * Untreated aortic stenosis can lead to hypertrophic cardiomyopathy, dysrhythmias, myocardial infarction, and heart failure **Clinical Manifestations:** gradual development * angina, syncope, dyspnea * decreased SV and narrowed pulse pressure * slow HR, delayed pulses * crescendo-decrescendo systolic heart murmur (due to resistance to flow) heard best at R parasternal 2nd ICS **Diagnosis:** echo - used to assess severity of valvular obstruction before sx onset **Treatment:** vasodilator therapy; surgical valve replacement (severe cases)

Answer 234

**Description:** impairs blood flow from LA to LV; most common form of rheumatic heart disease **Etiology:** Autoimmunity in response to group A β-hemolytic streptococcal M protein antigens leads to inflammation and scarring of the valvular leaflets → scarring causes leaflets to become fibrous and fused, chordae tendinae become shortened **Pathophysiology:** LA unable to fully empty leading to elevated atrial pressure (may eventually caused atrial dilation and hypetrophy) * high risk of developing a-fib and dysrrhythmia induced thrombi * as mitral stenosis progresses, CO decreases (especially on exertion) * continued elevation of left atrial pressure increases pressure in pulmonary circulation * if untreated, leadds to pulmonary hypertension, pulmonary edema, and R ventricular failure **Clinical Manifestations:** rumbling decrescendo diastolic murmur (heard best over cardiac apex and radiating to left axilla) * sharp noise: opening snape - when mitral valve is forced open during diastole * S1 (first heart sound) often accentuated and somewhat delayed due to increased left atrial pressure * pulmonary congestion * right heart failure **Diagnosis:** atrial enlargement and valvular obstruction (chest x-rays), ECGs, echos **Treatment:** anticoagulation therapy and HR control; repair with percutaneous balloon commisurotomy (open heart surgery) for valve replacement

Answer 235

**Descriptions:** result from inability of aortic valve cusp to close properly during diastole due to abnormalities of the cusps, aortic root and annulus, or both * can be primary (caused by congenital bicuspid valve or degeneration in elderly) * secondary (from chronic HTN, rheumatic heart disease, bacterial endocarditis, syphilis, connective tissue disorders, appetite suppressing meds, trauma, atherosclerosis) **Pathophysiology:** during systole, blood is ejected from LV into aorta; during diastole, some blood flows back into LV through leaking valve leading to volume overload (now receives blood from LA and aorta) * ↑ EDV of LV * myocardial fibers stretch to accommodate extra fluid * compensatory dilation permits LV to ↑SV and maintain CO * ventricular hypertrophy (to adapt to increased volume) - eventually cannot compensate and heart failure occurs **Clinical Manifestations:** widened pulse pressure (due to ↑SV and diastolic backflow) * decrescendo murmur in 2nd, 3rd, and 4th ICS parasternally, may radiate to neck * Corrigan pulse (prominent carotid pulsations and bounding peripheral pulses * HF symptoms (if ventricle can no longer pump adequately) * dysrrhythmias **Diagnosis:** ECHO to determine severity **Treatment:** vasodilators, inotropic meds, eventually valve replacement surgery

Answer 236

**Description:** characterized by mitral valve not closing properly leading to backflow of blood from LV into LA during ventricular systole * can be primary: due to mitral valve prolapse, rheumatic heart disease, infective endocarditis, MI, connecti tissue diseases, and dialted cardiomyopathy * secondary: due to ischemic or non-ischemic myocardial disease damaging chordae tendinae or mitral annulus **Pathophysiology:** increased LA volume causes LV to become dilated and hypertrophied to maintain adequate CO * backflow re-entering LA causes atrial dilation and associated a-fib * as LA enlarges, valve structures stretch and become deformed, leading to further backflow * eventually atrial pressure leads to pulmonary HTN and failure of RV **Clinical Manifestations:** holosystolic (throughout systole) murmur heard at cardiac apex radiating to back and axilla * mitral incompetence usually well tolerated until ventricle fials * most S/S caused by HF **Diagnosis:** ECHO - for severity **Treatment:** transcatheter, surgical repair, valve replacement

Answer 237

* more common than tricuspid stenosis * primary tricuspid regurgitation caused by congenital defects, rheumatic heart disease, endocarditis, or trauma * 80% of cases are functional * leads to volume overload in RA and RV, increased systemic venous BP, right HF * pulmonic valve dysfunction can have same consequences as this

Answer 238

**Description:** one or both cusps of mitral valve billow upward (prolapse) into LA during systole; mitral regurgtation occurs if ballooning valve permits blood to leak into atrium **Cause:** most common - myxomatous degeneration of leaflets in which cusps are redundant, thickened, and scalloped (due to changes in tissue proteoglycans, increased levels of proteinases, and infiltration by myofibroblasts) * potential combo of genetic x environment disruption of valvular development during 5th/6th week of gestation **Prevalence:** most common valve disorder in US **Clinical Manifestation:** many can be asymptomatic; * if symptomatic: palpitations, tachycardia, lightheadedness, syncope, fatigue (especially in the morning), lethargy, weakness, dyspnea, chest tightness, hyperventilation, anxiety/depression, panic attacks, and atypical chest pain * vague sx **Dx:** cardiac auscultation on physical exam + echo **Treatment:** excellent prognosis, do not develop symptoms, and do not require any restriction in activity or medical management; occasional need for B-blockers to alleviate syncope, severe chest pain, or palpitations

Answer 239

**Description:** systemic, inflammatory disease caused by a delayed exaggerated immune response to infectio by _group A β-hemolytic streptococcus_ in genetically predisposed individuals * ^ acute form is a febrile illness characterized by inflammation of the joints, skin, nervous system, and heart * if untreated, can cause scarring and deformity of cardiac structures, resulting in **rheumatic heart disease (RHD)** ~10% of ppl **Prevalence:** most often in children (5-15); RHD peak incidence 25-34 **Pathophysiology:** can develop _only_ as a sequel to pharyngeal infection by group A β-hemolytic streptococcus * fever is a result of an abnormal humoral and cell-mediated immune response to group A streptococcal cell membrane antigens called M proteins * immune response cross-reacts with similar self-antigens in heart, msucle, brain, and joints leading to autoimmune response * results in diffuse, proliferative, exudative inflammatory lesions in ^ tissues * rheumatic fever primarily causes endocardial inflammation causing swelling of valve leafles and erosion along cusp lines * clumps of vegetation (platelets x fibrin) deposit on valvular tissue and chordae tendinae * Scarring and shortening of the involved structures occur over time; valves lose their elasticity, and the leaflets may adhere to each other * may cause myocarditis, leading to fibrin necrotic bodies (Aschoff bodies) * Cardiomegaly and left heart failure may occur during episodes of untreated acute or recurrent rheumatic fever * Conduction defects and atrial fibrillation often are associated with rheumatic heart disease. **Clinical Manifestations:** common symptoms (fever, lymphadenopathy, athralgia, N/V, epistaxis, abdo pain, tachycardia) * Major S/S: usually occur singly or in combination 1-5 weeks post strept infection * carditis: murmurs, chest pain, friction rub, ECG changes, valvular dysfunction * acute migratory polyarthritis: heat, redness, swelling, pain amon large joints * chorea (irreg. movements) * erythema marginatum (nonpruritic macules; pink ring rashes on trunk but not faces/hands; fades in center) * subQ nodules - palpable over bony prominences and extensor tendons **Dx:** +ve throat cultures of group A β-hemolytic streptococci; measuring serum antibodies; elevated WBC, EST, and CRP (indicate inflammation) **Treatment:** Appropriate antibiotic therapy given within the first 9 days of group A β-hemolytic streptococcus infection usually prevents rheumatic fever * 10 day oral penicillin or erythromycin * NSAIDs used as anti-inflammtory agents (for rheumatic carditis and arthritis) * severe carditis may need corticosteroids, diuretics * continued prophylactic antibiotic therapy (due to recurrent nature of condition)

Answer 240

**Description:** general term used to describe infection and inflammation of endocardium **Causes:** most common cause - BACTERIA (esp. streptococci, staphylococci, and enterococci); others are viruses, fungi, rickettsia, parasites * Risk factors: acquired valvular heart disease; implantation of prosthetic heart valves; congenital lesions assocaited with highly turbulent flow; previous attack of infective endocarditis; IV drug use; LT indwelling catheter **Pathophysiology:** three critical elements: 1. **Endocardial damage:** most commonly by trauma, congenital heart disease, valvular heart disease and presence of prosthetic valves → exposes endothelial basement membrane → platelets attracted = thrombus formation → inflammatory reaction (**non-bacterial thrombotic endocarditis**) 2. **Adherence of blood-borned microorganisms to damaged endocardial surface:** bacteria entering bloodstream via IV drug use, trauma, dental procedures, indwelling catheters, surgery, resp./skin entry routes → they adhere to damaged endocardium using adhesins 3. **Formation of infective endocardial vegetations:** bacteria infiltrate thrombi and activate clotting cascade, and protected by fibrin clot so can't be killed → formation of vegetation → embolization from these vegetations can lead to abscesses and skin changes (petechiae, splinter hemorrhages, Osler node, Janeway lesions) **Clinical Manifestations:** classic findings - fever (80% of cases); new or changes cardiac murmur; petechial lesions of skin, conjunctiva, oral mucosa * Characteristic physical findings: Osler nodes (painful erythematous nodules on pads of fingers/toes); Janeway lesions (nonpainful hemorrhagic lesions on palms/soles) * CNS complications: stroke, abscess, meningitis * weight loss, back pain, night sweats, heart failure **Diagnosis:** Duke criteria (repetitive blood cultures positive for bacteria + evidence for endocardial involvement i.e. murmurs, regurgitation); recognized risk factors, fever, vascular complications; elevated CRP; ECHO **Treatment:** antimicrobial therapy (starts with IV, ends with oral admin) - or two antibiotics to prevent drug resistance * surgery to excise infected tissue

Answer 241

* those with HIV and AIDS are at risk for cardiac complications * dilated cardiomyopathy * myocarditis * pericardial effusion * endocarditis * pulmonary HTN * non-antiretroviral drug-related cardiotoxicity * treatment with antiretroviral therapy can cause hyperlipidemia and atherosclerotic disease * left HF - MOST COMMON complication of HIV infection; related to left ventricular diltation and dysfunction and sudden death

Answer 242

* when the heart is unable to generate an adequate CO, causing inadequate tissue perfusion or increased diastolic filling pressure of the LV, or both, so that pulmonary capillary pressures are increased * most common reason for admission to the hospital in 65+ * most important predisposing risk factors: ischemic heart disease and HTN * other risk factors: age, obesity, diabetes, renal fialure, valvular heart disease, cardiomyopathies, myocarditis, congenital heart disease, and excessive EtOH use * Most causes of heart failure result from _dysfunction of the LV_ (heart failure with reduced EF and heart failure with EF) * RV also may be dysfunctional, especially in pulmonary disease (RV failure)

Answer 243

* two categories (one person can have both at the same time): * **Heart failure with reduced EF (HFrEF)/systolic heart failure** * **Heart failure with preserved EF**

Answer 244

* aka **systolic heart failure** * defined as EF \<40% and inability of heart to generate adequate CO to perfuse vital tissues **Pathophysiology** * ↓ contractility - caused by MI (primary cause), myocarditis, cardiomyopathies * causes of ↓ contractility also mediate **ventricular remodeling** (results in disruption of normal myocardial extracellular structure with resulting dilaiton of myocardium and progressive mycocyte contractile dysfunction over time) * ∴ ↓ SV and ↑ LVEDV (increased preload with decreased contractility or excess plasma volume) * ↑ LVEDV can improve CO to an extent but as preload continues to rise, myocardium is stretched and will eventually lead to dysfunction of sarcomeres and decreased contracility (Frank-Starling law) * ↑ afterload (due to ↑ PVR) causes more workload for the ventricle (so it hypertrophies) = ↑ oxygen demand by myocytes * as CO falls, renal perfusion ↓ with activation of RAAS - this increases PVR and plasma volume which only further icnreases afterload and preload * baroreceptors in central circulation also detect decrease in perfusion and stimulate SNS to cause vasoconstriction and signal hypothalamus to make ADH

Answer 245

**Clinical Manifestations:** dyspnea, orthopnea, cough of frothy sputum, fatigue, decreased urine output, edema **Diagnosis:** pulmonary edema (cyanosis, inspiratory crackles, pleural effusions) on physical exam; hypotension/HTN; S₃ gallop; evidence of underlying CAD/HTN * ECHO shows pulmonary congestion with cardiomegaly **Treatment:** aimed at interrupting worsening cycle of decreasing contractility, increased preload, increased afterload * Oxygen, nitrate, morphine to improve myocardial oxygenation and relieve coronary spasm while lowering preload * inotropic drugs (dopamine, dobutamine, milrinone) to increase contractility and raise BP * diuretics - to reduced preload * ACE inhibitors, ARBs, aldosterone blockers - reduce preload and afterload by decreasing aldosterone level and reducing PVR * potential acute coronary bypass or PCI

Answer 246

**Description:** aka **diastolic heart failure** * results from decreased compliance of LV and abnormal diastolic relaxation causing ↑ LV end-diastolic pressure (LVEDP) even with normal LVEDV * pressure is reflected back into pulmonary circulation and results in pulmonary edema, pulmonary HTN, and RV hypertrophy * Causes: myocardial hypertrophy and ischemia, diabetes, valvular and pericardial disease **Pathophysiology** * HFpEF preceded by **preclinical diastolic dysfunction (PDD)** - ppl do not have sx but have early changes in ventricular relaxation and high untreated risk of develop heart failure * major causes of PDD - HTN-induced myocardial hypertrophy and myocardial ischemia-induced ventricular remodeling * ^ decrease ability of myocytes to actively pump Ca++ from cytosol ∴ impaired relaxation) * amount of LV stiffness and RV hypertrophy - **strongest** pathophysiologic predictors of complications from HFpEF * characterized by sustained activation of RAAS and SNS (similar to HFrEF)

Answer 247

**Clinical Manifestations:** dyspnea on exertion and fatigue * evidence of pulmonary edema (inspiratory crackles on auscultation, pleural effusions) is usually not present in resting individuals without tachycardia * S4 gallop * ECG shows left ventricular hypertrophy * Chest X-ray shows pulmonary congestion without cardiomegaly **Diagnosis:** based on 3 things - S/S of heart failure, normal LV EF, evidence of diastolic dysfunction (Dx confirmed with ECHO showing poor ventricular filling with normal EF) **Treatment:** improving ventricular relaxation and prolonging diastolic filling times to reduce diastolic pressure * no therapy has shown improvements in survival * statins has shown improvements in LV diastolic function; similar poor outcome as HFrEF

Answer 248

**Description:** inability of RV to provide adequate blood flow into pulmonary circulation at a normal central venous pressure * can result from left HF when an increase in LV filling pressure is reflected back into pulmonary circulation * as resistance in lungs increase, resistance to right ventricle emptying increases * RV cannot compensate for increased afterload and will dilate and fail * venous system pressure rises * If RHF occurs while LHF doesn't, cause is due to diffuse hypoxic pulmonary disease (COPD, CF, ARDS) which all increased RV afterload * Other causes: MI, cardiomyopathies, and pulmonic valvular disease can interfere with RV contractility leading to RHF **Clinical Manifestations:** peripherla edema; hepatosplenomegaly **Treatment:** management of left ventricular dysfunction (in left HF)

Answer 249

**Description:** inability of heart to adequately supply body with blood-borne nutrients, despite adeuqate blood volume and normal or elevated myocardial contractility * heart increases its output but body's metabolic needs are still not met **Cause:** common causes - anemia, septicemia, hyperthyroidism, beriberi (thiamin/B1 deficiency) **Pathophysiology:** * _Anemia:_ ↓ oxygen carrying capacity of blood, causing tissue hypoxia and anaerobic metabolism kicking in → metabolic acidosis occurs → HR and SV ↑ to improve tissue perfusion (if severe, even max CO can't help) * _Septicemia:_ cause systemic vasodilation and fever → SVR ↓ while metabolic rate ↑ which causes CO ↑ to maintain BP and prevent metabolic acidosis (if severe, CO cannot compensate for vasodilation) * _Hyperthyroidism:_ accelerates cell metabolism through ↑ levels of thyroxine from thyroid gland → increased oxygen demand threatens to cause metabolic acidosis so body increases CO (if ++thyroxine and metabolic response is vigourous, elevated CO may be inadequate) * _Beriberi:_ thiamine deficiency usually 2' to malnutrition (from alcoholism) → deficiency impairs cell metabolism in all tissues leading to insufficiency contractile strength; also causes peripherla dilation (↓SVR) → triggered to increased CO but impaired myocardium is unable to deliver it

Answer 250

hypoperfusion

Answer 251

when CV system fails to perfuse tissues adequately, resulting in widespread impairment of cellular metabolism; various causes and clinical manifestations progresses to organ failure and death (unless compensatory mechanism reverse the process or clinical interventions succeeds)

Answer 252

impairment of cellular metabolism

Answer 253

* cell shifts to anaerobic metabolism (and cell begins to use ATP stores faster than can be replaced) * cell cannot operate Na+/K+ pump * sodium and chloride accumulation inside the cell, potassium exits the cell * immediate effect on CNS and myocardium * water from interstitial space follows sodium into the cell → water from vascular space to be drawn out into the interstitial space to "replace" the water → ↓ circulatory volume * cellular edema disrupting cell membranes and causing release of lysosomal enzymes → internal cell damage and the leakage into interstitial space * **Compensatory mechanisms:** inflammation and activation of clotting cascade (but these further impair oxygen use) * contributes to complications of shock ex. acute tubular necrosis (ATN), ARDS, and DIC * anaerobic metabolism also ↓ pH = metabolic acidosis develops * **Compensatory:** enabling cardiac and skeletal muscles to use lactide acid as a fuel source for a limited period of time * enzymes dissociate under acidic conditions → cell function, repair and division is stopped * ↓ pH also reduces oxygen-carrying capacity of blood ∴ ↓ oxygen delivered to cells * further acidosis triggers release of moe lyososomal enzymes

Answer 254

* reasons for inadequate glucose delivery are similar to those for inadequate oxygen delivery * in septic and anaphylactic shock, glucose metabolism may be increased/disrupted due to fever or bacteria, and glucose uptake can be prevented by presence of vasoactive toxins, andotoxins, histamine, and kinins * **Compensatory mechanisms:** cause decreased glucose uptake by cells * high levels of cortisol, thyroid hormone, and catecholamines contirbute to hyperglycemia and insuling resistance * cells shift to glycogenolysis, gluconeogenesis, and lipolysis to generate fuel for survival (causing decrease in energy stores) * gluconeogenesis causes ↑ pyruvate which ↑lactate (and similar processes in impaired oxygen of metabolic acidosis, pH changes etc.)

Answer 255

* protein depletion is also a cause of organ failure * gluconeogenesis causes proteins to be used for fuel → proteins no longer availabel to maintain cell structure, function, repair, and replication * during anaerobic metabolism, protein metabolism liberates alanine which is converted to pyruvate → in sepsis, pyruvate turns into lactic acid and a positive feedback loop is formed * ammonia and urea byproducts also produed * uremia develops, and uric acid further disrupts cell metabolism * serum protein consumption ↓ capillary osmotic pressure and contributes to development of interstitial edema (creating another +ve feedback loop that decreases circulatory volume) * In septic shock, plasma protein breakdown includes metabolism of immunoglobulins, thereby impairing immune system function when it is most needed * muscle wasting (due to protein breakdown) also occurs, weakening skeletal and cardiac muscle (impaires muscles that facilitate breathing → impaired removal of waste products i.e. another +ve feedback loop)

Answer 256

buildup of metabolic end products in vell and interstitial spaces shock becomes irreversible once a sufficiently large number of cells from vital organs have damage to cellular membranes, leakage of lysosomal enzymes, and ATP depletion

Answer 257

* discover and correct/remove underlying cause & simultaneous management of improving microcircualtory tissue perfusion * IV fluids (to expand intravascular volume) * use of vasopressors and supplemental oxygen * control of glucose levels * further tx depends on cause and severity * once +ve feedback loops are established, intervention in shock is difficult

Answer 258

* **Cardiogenic:** caused by heart failure * **Hypovolemic:** caused by insufficient intravascular volume * **Neurogenic:** caused by neural alterations of vascular smooth muscle tone * **Anaphylactic:** caused by immunologic processes * **Septic:** caused by infection In carolyn's notes: * **Obstructive shock:** prevention of blood flow (obstruction i.e. embolism, PE) * **Distributive shock:** septic, anaphylactic, and neurogenic shock * excessive vasodilation and impaired distribution of blood flow (decreased tissue perfusion due to decreased SVR) * fluid collects beween cells of organs that require oxygen and the vessels that provide it, so oxygen can't move between the blood to organs (has to move through a lot of fluid to reach the tissues)

Answer 259

**1) Hypotension due to low CO (HR and SV)** - hypovolemic, cardiogenic, obstructive **2) Decrease in SVR** - all distributive shocks

Answer 260

**Stage 1 - Compensated Shock** * low perfusion first detected * multiple systems are activated to maintain/restore perfusion * ↑ HR, ↑ SVR, fluid retention by kidneys, maximized blood flow to most important organs and systems in the body * few Sx with this stage of shock * aggressive tx may slow progression **Stage 2 - Decompensated Shock** * compensation begins to fail * unable to improve perfusion any longer * oxygen deprivation in the brain causes patient to become confused and disoriented **Stage 3 - Irreversible Shock** * poor perfusion begins to take a permanent toll on body's organs and tissues * heart's functioning continues to decline * kidneys usually completely shut down * cellular injury and death * endpoint of Stage III shock is patient death 💀

Answer 261

**Description:** defined as decreased CO and evidence of tissue hypoxia in the presence of adequate intravascular volume (due to heart not being able to generate enough power) **Causes:** most cases follow MI; can also follow left HF, dysrhythmias, acute valvular dysfunction, ventricular/septal rupture, myocardial or pericardial infections, massive PE, cardiac tamponade, and drug toxicity * Myocarditis – inflammation of the myocardium * Multiple or severe MI’s causing scar tissue * Aortic or mitral valve stenosis - too much work, causing the heart to wear out from overwork * Tachydysrhythmias – going too fast, not allowing enough time for filling, decreased hr – not enough output and flow to cardiac muscle * Dilated cardiomyopathy – heart muscle is stretched out, doesn’t contract well enough – Starling’s law * Congenital heart disease – patent ductus arteriosis **Pathophysiology:** microcirculation changes within myocardium contributes to decreased contractility and worsening CO; compensatory neurohumoral reponses by RAAS, SNS, and ADH systems contribute to increased oxygen demands **Clinical Manifestations:** impaired mental activity, dyspnea and tachypnea, systemic venous and pulmonary edema, dusky skin colour (light brown), hypotension, oliguria (low urine output - kidneys retaining urine, reabsorbs Na+ and H₂O stimulating thirst), ileus (temp lack of movment in bowels) * fluid retention * metabolic acidosis - common pathway for all types of shock * cyanosis * hypoxia, low Spo₂ **Treatment:** oxygen * careful fluid (NaCl fluid bolus) and vasopressor administration (+ve ionotropic to increase contractility and SVR - epi, atropine, dopamine) * treat underlying causes (MI - angioplasty; thrombolytics, need for PCI, etc.) * **Note: this type of shock is often unresponsive to tx with high mortality rates**

Answer 262

**Description:** caused by loss of whole blood (hemorrage), plasma (burns), or interstitial fluid (diaphoresis, DM, diabetes insipidus, emesis, diarrhea, diuresis) in large amounts * hypovolemic shock begins to develop when intravascular volume has ↓ by ~15% * lower perfusion and low BP due to low volume in vasculature **Causes:** * **Blood loss (low Hct):** GI bleed, AAA rupture, trauma, postpartum hemorrhage, ectopic pregnancy, hemoptysis (esophageal/pulmonary varices) * **Non-blood fluid loss (High Hct):** 3rd degree burns, excessive vomiting, diarrhea, bowerl obstruction (decreased intake so pulls fluid into GI out of tissues), pancreatitis (overactive enzymes digesting pancreatic tissue causing tissue to leak out), DKA (sugar can't be absorbed so takes water with it when excreted in urine) **Pathophysiology:** hypovolemia initially offset by compensatory mechanisms (HR and SVR increased to increase CO and tissue perfusion * **Intialy compensations:** IF moves into vascular compartment; liver and spleen add to vlood volume by release stored RBCs and plasma; renin stimulates aldosterone release (sodium retention and thus water) * **Compensation eventually fails:** decreased tissue perfusion leading to impaired cellular metabolism **Clinical manifestations:** high SVR poor skin turgor, oliguria (poor urine output), low systemic/pulmonary preloads, hypotension, tachycardia, thready pulse, mental status deterioration, cyanosis, hypoxia - low SpO₂ **Treatment:** rapid fluid replacement with crystalloids and blood products (Ringer's Lactate; N. Saline); ADH to improve BP in those with hemorrhagic hypovolemic shock) * maintain temperature * plasma volume expanders (i.e. albumin) * surgical repair of problem, antibiotics

Answer 263

**Description:** aka **vasogenic shock;** the result of widespread and massive vasodilation that results from parasympathetic overstimulation and sympathetic understimulation **Cause:** can be caused by factor that stimulates parasympathetic or inhibits sympathetic stimulation of vascular smooth muscle * trauma to spinal cord or medulla * conditions that interrupt oxygen/glucose supply to medulla * depressive drugs, anesthetic agents (autonomic block), severe emotional stress, pain **Pathophysiology:** loss of vascular tone results in "relative hypovolemia" (blood volume hasn't changed by SVR is decreased so that the amount of space containing the blood has increased) - unable to regulate due to unopposed vagal tone * pressure in vessels decreases below what is needed to drive nutrients across capillary membranes to the cells * neurologic insult may cause bradycardia which decreases CO and further contributes to hypotension and underperfusion of tissues **Clinical Manifestations:** bradycardia, vasodilation due to decreased SVR, hypotension, hypoxia, ischemia, necrosis, loss of vasomotor tone **Treatment:** careful use of fluids and vasopressors until BP stabilizes

Answer 264

**Description:** results from widespread hypersensitivity rxn (anaphylaxis) **Causes:** exposure of sensitized individual to an allergen * Common allergens: insect venoms (bee stings), shellfish, peanuts, latex, and meds such as penicillin * IV contrast dyes * temperature/exercise induced anaphylaxis * higher risk for food allergies for those with asthma, eczema, allergic rhinitis * usually not first exposure **Pathophysiology:** same as neurogenic shock - vasodilation and relative hypovolemia leading to decreased tissue perfusion and impaired cellular metabolism * In genetically predisposed individuals, these allergens initiate vigorous humoral immune response (type I hypersensitive reaction) resulting in large production of IgE → allergen binds to IgE → degranulation of mast cells → release of vasoactive and inflammatory cytokines (like histamine)→ inflammatory response (vasodilation, increased vascular permeability leading to peripheral pooling and tissue edema) * extravascular effects: constriction of extravascular smooth muscle (often causing laryngospasm and bronchospasm/bronchoconstriction = resp distress) and cramping abdo pain with diarrhea **Clinical Manifestations:** sudden onset and quick progression to death within minutes unless emergency treatment is given * anaphylaxis: anxiety, dizziness, difficulty breathing, stridor, wheezing, pruritis with hives, swollen lips and tongue, and abdo cramping * anaphylactic shock: decreased BP, tachycardia, impaired mental status, decreased SVR (with high/normal CO), oliguria * feeling of impending doom **Diagnosis:** confirmation via serum markers (histamine, tryptase) **Treatment:** removal of antigen; epinephrine 1:1000 IM to cause vasoconstriction and reverse airway constriction) * Benadryl (Diphenhydramine) * Ranitidine (blocks effects of histamine - reverse vasodilation) * IV fluids to reverse relative hypovolemia * antihistamines & corticosteroids (to stop inflammatory reaction) * vasopressors and inhaled β- adrenergic agonist bronchodilators * oxygen * prevention!

Answer 265

**Description:** an internal/external obstruction of the blood flow into/out of the heart, chamber or great vessels **Causes:** * tension pneumo (blood builds up between pleura, pushing on lung and heart puting pressure on vena cava and aorta reducing flow) * pericardial tamponade (Beck's Triad - HVD, hypotension, muffled heart sounds) - fluid pressing on outside of heart which compresses it (heart doesn't fill or contract properly) * massive PE - embolism blocking pulmonary artery, preventing blood from returning to LV * Saddle embolism: when a large blood clot gets stuck in the main pulmonary artery (pulmonary trunk) **Clinical Manifestations:** JVD, tracheal deviation, cyanosis, respiratory distress, elevated lactic acid levels, muffled herat tones, hypoxia, absent lung sounds **Treatment:** oxygen!; IV fluids, needle decompression, pericardiocentesis, thrombolytics

Answer 266

presence of viable bacteria in blood

Answer 267

**Sepsis:** systemic response to infection characterized by 2+ SIRS criteria **Severe Sepsis:** Sepsis associated with organ dysfunction **Septic Shock:** severe sepsis complicated by persistent hypotension refractory to early fluid therapy (circulatory collapse)

Answer 268

**Description:** begins with an infection that progresses to bacteremia and eventually SIRS (Systemic Inflammatory Response Syndrome) with sepsis, then severe sepsis, then septic shock, finally multiple organ dysfunction syndrome (MODS) **Causes:** community-acquired or healthcare-associated infections (esp. pneumonia, intra-abdominal, and UTIs) * indwelling arterial and central venous catheters - source of infection * Central line-associated bloodstream infection (central lines used for administering medications, hemodialysis, monitoring hemodynamics) * increased risk of CLABSI with age, underlying conditions, catheter-related factors (# of catheters, site of insertion, length of time catheter is in place) * most common gram+ve: *Staph aureus; Strept. pneumoniae* * most common gram-ve: *E. coli; Klebsiella; Pseudomonas aeruginosa* * fungi, viruses * chemotherapy * dysuria (painful urination) * burns, infected wounds, cellulitis * **Risk factors:** genetic composition, underlying chronic disease, immune deficiency states, timeliness of medical intervention **Pathophysiology:** starts with bacteremia - toxins initiate an innate immune response * Gram-ve - releases endotoxins * gram+ve releases exotoxins, lipoteichoic acids, peptidoglycans * trigger septic syndrom by interacting with Toll-like receptor 2 (TL2 for gram+ve) and TLR-4 (for gram-ve) * release of inflammatory mediators & complement, coagulation, kinins, and inflammatory cells also activated → triggers subsequent release of secondary mediators (cytokines, complement fragments, prostglandins, PAF, oxygen free radicals, NO, proteolytic enzymes) * systemic inflammation occurs, leading to widespread vasodilation (esp due to NO) with compensatory tachycardia and increased CO (early stages of septic shock - **warm shock/****hyperdynamic phase**) * progression in disease leads to inflammatory mediators depressing myocardial contractility (CO ↓, tissue perfusion ↓) - **cold shock** * ^ leads to SIRS - which can further progress to widespread tissue hypoxia, necrosis, and apoptosis leading to septic shock and MODS **Clinical Manifestations:** * early shock: tachycardia and normal/elevated CO * temperature instability (hyperthermia to hypothermia) * deranged renal function, jaundice, clotting abnormalities with DIC/microvascular occlusions/clotting * deterioration of mental status, ARDS * GI mucosa changes: translocation of bacteria from gut into bloodstream (increased gut permeability can lead to increased inflammation and immune reactions) * mottled extremities, poor cap refil **Diagnosis:** recognition of SIRS manifestations ; additional measures: serum lactate, troponin levels, CRP, procalcitonin **Treatment:** fluids, vasopressors (NE, vasopressin), antibiotics, respiratory support (positioning, ventilation), Tylenol/Advil * insulin (for hyperglycemia) * nutritional support * prevention of stress ulcers and DVT

Answer 269

SIR - 2 or more of 4 criteria * temp \> 38°C or \<36°C * HR \>90 BPM * RR \> 20 breaths per min or PaCO₂ level \< 32mmHg * WBC \> 12 000 cells/mm³, \< 4000 cells/mm³ or containing M10% immature forms (bands)

Answer 270

**Description:** progressive dysfunction of two or more organ systems resulting from uncontrolled inflammatory repsonse to a severe illness or injury; frequent complication of severe shock and can progress to organ failure and death **Causes:** most common - sepsis and septic shock * any severe injury/disease process that activates massive systemic inflammatory response can initiate MODS (severe trauma, burns, acute pancreatitis, obstetric complications, major surgery, circulatory shock, some drugs, and gangrenous/necrotic tissue) * Other common triggers: acute renal failure, liver failure, ARDS, blood transfusion, heat stroke, mesenteric ischemia, necrotic tissue, DIC **Prevalence:** common cause of mortality in ICUs; 36-100% mortality rate if failure of 5+ organs * liver and kidney failure most common * **Risk Factors:** elderly, persons with significant tissue injury, preexisting disease **Pathophysiology:** initial insult activates neuroendocrine system to release stress hormones (cortisol, E, NE) into bloodstream * vascular endothelial damage - direct result of injury/damage from bacteria and inflammatory mediators → ↑ endothelial injury → allows fluid and protein leak into interstitial spaces → hypotension and hypoperfusion * leakage of fluid in lungs causes ARDS * damaged endothelium activates platelets and tissue thromboplastin reuslting in microvascular coagulation (which may lead to DIC) * release of inflammatory mediators activates: complement, coagulation, fibrinolytic, and kallikrein/kinin (overall effect: hyperinflammatory and hypercoagulant state that maintains interstitial edema formation, CV instability, endothelial damage, and clotting abnormalities characteristic of MODS) * massive systemic immune/inflammatory response develops involving neutrophils, macrophages, mast cells ⇒ leads to **hypermetabolism** and maldistribution of blood flow * oxygen delivery to tissues decreases despite supranormal systemic blood flow because: * 1) blood shunted past selected regional capillary beds (due to inflammatory mediators overriding normal vascular tone) * 2) interstitial edema - result of microvascular changes in permability (relative hypovolemia & increases distance oxygen must travel to reach cells) * 3) capillary obstruction - occurs due to formation of microvascular thrombi and WBC aggregation * **Compensatory:** is the hypermetaoblism to meet body's increased demands for energy (but net result is oxygen and fuel supply depletion) * myocardial depression also occurs * Maldistribution of blood flow, coagulation, myocardial depression, ARDS, and the hypermetabolic state combine to create an imbalance in oxygen supply and demand (results in condition called **supply-dependent oxygen consumption** - this is where oxygen consumed is dependent on the amount that circulation is able to deliver and not by how much cells need) * tissue hypoxia with cellular acidosis and impaired cellular function occur - results in multiple organ failure **Clinical Manifestations:** there may be a lag time between inciting event and sx onset (up to 24 h) * low grade fever, tachycardia, dyspnea, altered mental status, hyperdynamic and hypermetabolic states * **Respiratory:** ARDS - early manifestation of MODS - tachypnea, pulmonary edema with crackles and diminished breath sounds, use of accessory muscles, hypoxemia * **Hepatic:** progression leads to liver failure (jaundice, abdo distension, liver tenderness, msucle wasting hepatic encephalopathy) * impaired metabolism * **Renal failure:** progressive oliguria, azotemia (increased urea nitrogen levels), edema; potentially anuria (no urine), hyperkalemia, metabolic acidosis * **GI** dysfunction: hemorrhage, ileus, malabsorption, diarrhea/constipation, vomiting, anorexia, abdo pain, stress ulcers, bacteria translocation (moves into portal circulation and overwhelms liver; then moves into systemic circulation = sepsis) * Later manifestations: hematologic failure and myocardial failure (similar sx as septic shock) * Terminal stages: hypodynamic circulation with bradycardia, profound hypotension, and ventricular dysrhythmias * Encephalopathy, characterized by mental status changes ranging from confusion to deep coma, may occur at any time * **CNS manifestations** (caused by ischemia/inflammation): apprehension, confusion, disorientation, restlessness, agitation, headache, decreased cog. ability and memory, altered LOC * seizure coma death bb (14 days to several weeks of sx onset) **Diagnosis:** Acute Phsyiology and Chronic Health Evaluation II and III systems to assess severity and progression of MODS; monitoring lab values and hemodynamic parameters **Treatment:** no specific treatment; management: prevention and support * Prevention/Support: control initial insult, quick tx of infections, supporting healing * restore oxygen and perfusion, support organ function * antibiotics * ventilatory support * fluids * nutritional support * potential dialysis

Answer 271

congenital

Answer 272

congenital heart disease (CHD)

Answer 273

**1) maternal conditions** - intrauterine viral infections esp. rubella; DM, phenylketonuria (amino acids in urine), alcoholism, hypercalcemia, drugs, & complications of increased age **2) antepartal bleeding -** bleeding from the vagina that occurs after the 20th week of pregnancy **3) prematurity**

Answer 274

* often unknown mechanism * incident of CHD is 3-4x higher in siblings of affected children * chromosomal defects, associated with incresed incident of heart defects: * Down syndrome * trisomies 13 and 18 * Turner syndrome * cri du chat syndrome (chromosome 5p deletion syndrome)

Answer 275

1) whether the defect causes cyanosis 2) whether the defect causes increased/decreased blood flow into pulmonary circulation 3) whether the defect causes obstruction of blood flow from ventricles

Answer 276

abnormal movement of blood from one side of the heart to the other

Answer 277

* Shunting of blood flow from left heart into right heart * occurs in conditions: Atrial Septal Defect (ASD), ventricular septal defect (VSD) * increases pulmonary blood flow (blood continues to flow through lungs before passing into systemic circulation) = no decrease in tissue oxygenation or cyanosis * ∴ Left-to-right shunt: **acyanotic heart defects**

Answer 278

two types: **1) increased pulmonary blood flow** (left to right shunt) - ASD, VSD, PDA, AV canal **2) obstruction to blood flow from ventricles** (no shunting) - Coarctation of Aorta, aortic stenosis, pulmonic stenosis

Answer 279

* shunting of blood from right to left side of heart * decreases blood flow through pulmonary sysem causing less than normal oxygen delivery to tissues = cyanosis * **cyanotic heart defects**

Answer 280

Two types: **1) decreases pulmonary blood flow** - Tetralogy of Fallot, tricuspid atresia **2) mixed blood flow** - transposition of great arteries; total anomalous pulmonary venous return; Truncus arteriosus; hypoplastic left heart syndrome

Answer 281

Tetralogy of Fallot (TOF) - occurs in 5-10% of all CHD narrowing of pulmonary outflow tract increases right heart pressure thus forcing blood throuhg a defect in the ventricular septum into the left heart

Answer 282

* a bluish discoloration of the skin indicating that tissues are not receiving normal amounts of oxygen * also can be caused by other types of heart defects that result in the mixing of venous and arterial blood that enter the systemic circulation

Answer 283

* aka ductus Botalli * normal fetal artery connecting the main body artery (aorta) and the main lung artery (pulmonary artery) * allows most of the blood from the right ventricle to bypass the fetus's fluid-filled non-functioning lungs * closes within 15 h of birth

Answer 284

**Description:** Abnormal localized narrowing of the aorta just proximal to the insertion of the ductus arteriosus * before birth, ductus arteriosus bypasses this obstruction and allows for blood to flow from pulmonary artery into distal aorta * once ductus functionally closes within 15 hours of birth, blood flow to LE is restricted by coarctation **Clinical Manifestations:** * increased BP proximal to defect (head, UE, right \> left) and decreased BP distal to obstruction (torso, LE) * location and severity of COA determines whether infant will become symptomatic after ductus arteriosus closes * if severe: low CO, poor tissue perfusion, acidosis, hypotension * Physical findings: weak/absent femoral pulses * some remain asymptomatic despite closure of ductus arteriosus but as they age, childrehn will present with unexplained UE hypertension, leg pain, cramping with exercise * rare: dizziness, headaches, fainting, epistaxis **Evaluation/Diagnosis:** physical exam of UE and LE BP will often suggest diagnosis; ECHO, MRI, and cardiac catheterization may be needed **Treatment:** * Initial treatment (in symptomatic newborns): continuous IV infusion of prostaglandin E₁ to maintain patency of ductus arteriosus → surgical correction after stabilized * Surgery: reserction of narrowed portion of aorta with an end-to-end anastomosis OR enlargement of constricted section using graft (taken from L subclavian artery) * short-acting beta blocker for post-op HTN * Balloon angioplasty (complications: aneurysm formation and blood vessel injury)

Answer 285

**Description:** narrowing/stricture of LV outlet, causing resistance of blood flow from left ventricle into aorta; leads to hypertrophy of LV wall which eventually leads to increased end-diasolic pressure → pulmonary venous and arterial hypertension * decreased CO and pulmonary vascular congestion if severe * LV hypertrophy impedes coronary artery perfusion leading to potential subendocardial ischemia and associated papillary muscle dysfunction that cause mitral insufficiency **Types:** 3 types * **1)** **Valvular AS -** occurs due to malformed/fused cusps resulting in unicuspid/bicuspid valve; congenital but rare; serious defect because: * obstruction is progressive * may cause sudden episodes of myocardial ischemia or low CO that may lead to sudden death in late childhood or adolescence * surgical repair will not result in a normal valve * leads to reduction in strenuous activity that pt is able to do * **2) Subvalvular AS:** stricture caused by fibrous ring below a normal valve or a narrowed left ventricular outflow tract in combo with small aortic valve annulus * **3) Supravalvular AS:** narrowing of aorta just above the valve, occurs infrequently * can be due to single defect or as a part of Williams syndrome (elfin facial appearance) **Clinical Manifestations:** * infants: decrease CO with faint pulses, tachycardia, poor feeding * loud, harsh systolic ejection murmur * older children may have complaints of exercise intolerance and rarely chest pain * risk for bacterial endocarditis - blood borne pathogen can inhabit areas of the heart where there is high turbulence or reside on artificial material * α-hemolytic streptococci (most commonly found pathogen following dental or oral procedures * enterococci (most common bacterium found following genitourinary and GI tract surgery or instrumentation) * complications: coronary insufficiency, ventricular dysfunction, sudden death **Diagnosis:** confirmed with ECHO **Treatment:** no intervention or activity restriction (mild to moderate valvular AS) * initial tx of choice: nonsurgical palliation * balloon angioplasty * surgical tx depends on severity of stenosis, previous Ix, and age * Aortic valve commissurotomy (incision at the edges of joining point) or valvotomy * aortic valve replacement (if valve severely dysplastic) * Ross procedure: involves moving the native pulmonary valve (autograft) into the aortic position and replacing the pulmonary valve with an allograft (cadaver) * _Subvalvular AS:_ surgical correction - Konno procedure to correct (a patch to enlarge the entire left ventricular outflow tract and annulus and replace the aortic valve); incision the constrictive fibromuscular ring * _Supravalvular AS:_ balloon angioplasty and stent placement or surgical enlargement with coronary reimplantation

Answer 286

**Description:** narrowing/stricture of pulmonary valve that causes resistance to blood flow from RV to pulmonary artery; mod to severe stenosis cause RV hypertrophy * **Pulmonary atresia:** extreme form of PS with total fusion of valve leaflets (blood cannot flow to the lungs); RV may be hypoplastic **Clinical Manifestations:** many infants are asymptomatic if PS is mild to moderate * newborns with severe PS or pulmonary atresia become cyanotic (right-to-left shunt through through ASD); signs of decreased CO * harsh systolic murmur expected with PS * Pulmonary atresia produces continuous murmur **Diagnosis:** ECHO to confirm Dc and determine severity of the PS **Treatment:** for moderate to severe pulmonary stenosis: balloon angioplasty * may need surgical valvotomy * both options leave pulmonary valve incompetent (insufficient) but children are usually able to tolerate pulmonary valve incompetence and are asymptomatic

Answer 287

**Description:** failure of fetal ductus arteriosus (artery connecting aorta and pulmonary arery) to functionally close within first 15 hours after birth * allows blood to flow from the higher pressure aorta to the lower pressure pulmonary artery, causing a left-to-right shunt **Clinical Manifestations:** * infants may be asymptomatic or show signs of pulmonary overcirculation (dyspnea, fatigue, and poor feeding) * characteristic machinery-like murmur in both systole and diastole * aortic flow (run off) into lower pressure pulmonary circulation produces low DBP, widened pulse pressure, and bounding pulses * children at risk of bacterial endocarditis; may develop pulmonary HTN in later life from chronic excessive pulmonary blood flow **Diagnosis:** ECHO for confirmation **Treatment:** indomethacin (prostaglandin inhibitor) to close PDA in preemies * potential surgical thoracotomy * closure with an occlusive device for some \< 6mos

Answer 288

**Description:** an opening in the septal wall between the two atria, allow blood to shunt from left to right; three types: 1. **Ostium primum ASD:** opening low in atrial septum, may be associated with abnormalities of the mitral valve 2. **Ostium secundum ASD:** opening in the middle of the atrial septum; most common type 3. **Sinus venosus ASD:** opening usually high in atrial wall near junction of SVC; may be associated with partial anomalous pulmonary venous connection **Clinical Manifestations:** * Children: usually asymptomatic * Infants with large ASD may have: pulmonary overcirculation and slow growth (but rare) * Some older children/adults: SOB with activity as RV becomes less compliant with age * pulmonary HTN and stroke - associated rare compications * A systolic ejection murmur and a widely split second heart sound are the expected findings on physical examination **Diagnosis:** ECHO **Treatment:** ASD may be closed surgically with primary repair (suture closed) or with a patch (pericardium or Dacron) - via open heat surgery or catheterization device closure (less invaseive)

Answer 289

* an opening in atrial septal wall that is part of normal fetal communication and usually closes after birth * when lungs become functional at birth, pulmonary pressure decreases and left atrial pressure exceeds that of the right which forces septum to functionally close the foramen ovale * it if does not close, it is a **patient foramen ovale (PFO****)** * 1 in 4 adults have PFO without CHD but in children with CHD, foramen ovale often remains open

Answer 290

**Description:** an opening of the septal wall between the ventricles; most common type of congenital heart defect and account for 15-20% of all such defects; left-to-right shunt * Classified by location * **Perimembranous VSDs:** located high in ventricular septal wall underneath AV valves * **Muscular VSDs:** located low in septal wall * VSDs can also be located in inlet/outlet portions of ventricle * depending on size and location, many can close spontaneously (most often within first 2 years of life) **Clinical Manifestations:** depends on size, location, degree of shunting and pulmonary vascular resistance * may be asymptomatic or have clinical excessive pulmonary blood flow * infant: excessive pulmonary blood flow causes dyspnea, tachypnea * holosystolic (pansystolic) murmur * Complications (if shunting not corrected): risk of pulmonary HTN * irreversible HTN cause result in **Eisnmenger syndrome** (shunting of blood is reversed due to high pulmonary pressure and resistance - right to left shunt with cyanosis) **Diagnosis:** confirmed with ECHO; potential need for cardiac cath to calculate degree of shunting and measure pressures in heart **Treatment:** Minimal treatment for smaller VSDs which may close completely or small enough that surgery isn't required * for infants with severe HF/failiure to thrive, surgical repair needed (open heart surgery with bypass) - primary (suture closed) or coverd with a patched (pericardium or Dacron) * Nonsurgical devide closure * Endocarditis prophylaxis

Answer 291

**Description:** aka **atrioventricular septal defect (AVSD)/endocardial cushion defect (ECD);** the result of incomplete fusion of endocardial cushions * consists of ostium primum ASD and inlet VSD with associated abnormalities of AV valve tissue (such as cleft in mitral valve) * directions and pathways of flow are determined by pulmonary and systemic resistance, left and right ventricular pressures, and compliance of each chamber * flow generally left to right * common cardiac defect in children with Down syndrome **Clinical Manifestations:** moderate to severe HF due to left-to-right shunting and pulmonary overcirculation * infants with pulmonary HN and high pulmonary resistance have less shunting therefore minimal signs of HF * mild cyanosis that increases with crying * those with large left-to-right shunt will have a murmur * those with minimal shunt may not have murmur * Complication: risk for developing irreversible pulmonary HTN if left surgically untreated **Diagnosis:** fetal ECHO **Treatment:** medical management of HF and nutritional supplementation * monitoring for S/S of failure to thrive * pulmonary artery banding (infants with severe sx) * most common: surgical repair (done between 3-6mos) to prevent irreversible pulmonary HTN - patch closure of septal defects and reconstruction of AV valve tissue * potential valve replacement if severe

Answer 292

**Description:** includes four defects - VSD, Pulmonary Stenosis (PS), overriding aorta and RV hypertrophy; the most common cyanotic heart defect * pathophysiology varies, depending on degree of PS, pulmonary and systemic vascular resistance to flow * RL shunt: if total resistance to pulmonary flow is \> systemic resistance * LR shift: if systemic resistance \> pulmonary resistance * PS decreases blood flow to lungs and thus the amount oxygenated blood that returns to LA * **Compensatory response** (to chronic severe hypoxia): polycythemia, development of collateral bronchial vessels, clubbing (enlargement of nail beds) **Clinical Manifestations:** some acutely cyanotic at birth; others progress to hypoxia and cyanosis gradually over first year of life as PS worsens * acute episodes of cyanosis and hypoxia can occur (**hypercyanotic/blue spells or "tet" spells**) - due to increased RL shunt; can occur during crying or after feeding * knee-chest position and mophine sulfate subQ/IV is common in treating tet spells (position provides PVR increases pressures in left heart and subsequent RL shunting; improves pulmonary perfusion) * Chronic cyanosis may cause clubbing of figners and poor growth in children * unrepaired TOF: risk of emboli, stroke, brain abscess, seizures, and LOS/sudden death following a "tet" spell **Diagnosis:** confirmed with ECHO **Treatment:** elective surgical repair done in first year of life * closure of VSD, resection of infundibular stenosis, application of pericardial patch to enlarge RV outflow tract (transannular patch) * in small infants who cannot undergo repair: palliative procedure to increase pulmonary blood flow and increase O2 sats (Blalock-Taussig shunt)

Answer 293

**Description:** failure of tricuspid valve to develop; consequently no communication from right atrium to right ventricle * blood flows through an ASD or PFO to left atrium OR * through VASD to right ventricle **Cause:** often associated with PS or transposition of the great arteries **Pathophysiology:** complete mixing of deoxy and oxygenated blood in left side of the heart, resulting in systemic desaturation and mild cyanosis * variable physiologic process (depends on great vessel anatomy and amount of pulmonary stenosis) **Clinical Manifestations:** murmur; cyanosis in newborn * tachycardia, dyspnea, fatigue, and poor feeding may be noted with excessive pulmonary blood flow * older children: signs of chronic hypoxemia with clubbing * risk for bacterial endocarditis, brain abscess and stroke **Diagnosis:** echo **Treatment:** neonate with decreased pulmonary blood flow is treated with continuous infusion of prostaglandin E1 to maintain patency of ductus arteriosus until surgery * 1st stage: Blalock Taussig shunt (connecting systemic and pulmonary artery) to increase blood flow to lungs * 2nd stage: bidirectional Glenn shunt (SVC is connected with pulmonary artery) - may remove previous shunt * final stage: modified Fontan procedure - IVC is routed to pulmonary artery using a tube graft * **Post-op complications:** pleural and pericardial effusions, elevated PVR, ventricular dysfunction

Answer 294

**Description:** pulmonary artery leaves LV and aorta exits RV * may have other defects (ASD, VSD, or PDA) that permit mixing of saturday and desaturated blood that maintains adequate tissue oxygenation for a limited time * creates two parallel but separate circuits * unoxygenated blood circulates continuously through systemic circulation * oxygenated blood circulates continuously through pulmonary circulation **Clinical Manifestations:** depends on type and size of associated defects * children with limited communicatio b/w cardiac chambers are severely cyanotic, acidotic, and ill at birth * large septal defects or a PDA may be less severely cyanotic but may have Sx of pulmonary overcirculation * no murmur unless there is associated VSD **Diagnosis:** physical exam and confirmation via ECHO **Treatment:** IV prostanglandin E1 to keep ductus arteriosus open to temporarily increase oxygen delivery * arterial switch procedure: transecting great arteries and connecting main pulmonary artery to native proximal aorta (just above aortic valve) and connecting ascending aorta to native proximal pulmonary artery; reimplantation of coronary arteries * re-establishes normal circulation (LV being systemic pump) * potential complications: narrowing of great artery anastomoses, neoaortic valve regurgitation, coronary artery insufficiency

Answer 295

**Description:** rare defect characterized by failure of pulmonary veins to join LA during cardiac development; pulmonary venous return is connected to right side of circulation rather than to left atrium **Types:** classified ccording to pulmonary venous point of attachment: * **Supracardiac:** attachment above diaphragm, usually to SVC (most common form) * **Cardiac:** direct attachment to the heart, usually to RA or coronary sinus * **Infracardiac:** attachment below the diaphragm, such as IVC (most severe and least common form) **Pathophysiology:** RA receives all the blood that normally would flow out LA * causes right side of heart to be enlarged; left side smaller (esp. LA) * an associated ASD/PFO allows systemic venous blood to shunt from RA to left side of heart which causes oxygen saturation on both sides to be the same * if pulmonary blood flow is increased, pulmonary venous return is also large & amount of saturated blood is relatively high * if there is obstruction to pulmonary venous drainage, infant has severe cyanosis and low cardiac output (often seen in infracardiac TAPVS) **Clinical Manifestations:** most infants develop cyanosis early in life * degree of cyanosis is inversely relateed to amount of pulmonary blood flow * unobstructed TAPVC: may be asymptomatic until PVR decreases during infancy which increases pulmonary blood flow resulting in pulmonary overcirculation * cyanosis worsens with pulmonary vein obstruction - rapid deterioration and eventual cardiac failure if no tx **Diagnosis:** echo + angiography **Treatment:** corrective repair in early infancy (surgical repair varies with anatomical defect) however commonly pulmonary vein is sutured to left atrium, ASD is closed

Answer 296

**Description:** failure of normal separation/division of the embryonic artery and truncus arteriosus into pulmonary artery and an aorta; results in single vessel that exits the heart * always has associated VSD with mixing of the systemic and arterial circulations causing some degree of cyanosis * blood leaving the heart flows to lower pressure pulmonary arteries causing increased pulmonary blood flow **Types:** three types: 1. **Type I:** Single pulmonary trunk arises near base of truncus and divides into left and right pulmonary arteries 2. **Type II:** L and R pulmonary arteries arise separately from posterior aspect of truncus 3. **Type III:** pulmonary arteries arise independently and from alteral aspect of truncus **Clinical Manifestations:** most infants are symptomatic w/ moderate heart failure and varied cyanosis, poor growth, and activity intolerance; at risk of brain abscess and bacterial endocarditis **Diagnosis:** ECHO **Treatment:** corrective repair (modified Rastelli procedure) done within first few weeks/months of life * involves closing VSD so that truncus arteriosus receives outflow from LV * excise pulmonary arteries from aorta and attaching them to RV via cadaver graft (homograft) - to be replaced as child grows

Answer 297

**Description:** underdevelopment of left side of heart * features: small LA, small/absent mitral vale, small/absent LV, and small/absent aortic valve * coarctation (narrowing in aorta) expected * most blood from LA flows across PFO to RA → RV → pulmonary artery * descending aorta receives blood from PDA supply systemic blood flow and filling aorta + coronary arteries **Clinical Manifestations:** presents in early newborns as mild cyanosis, tachypnea, low CO * support of systemic circulation via prostaglandin E1 infusion * if HLHS not suspected and PDA closes, progressive deterioration occurs (cyanosis, decreased CO, leads to CV collapse) * if untreated, fatal within first months of life **Diagnosis:** ECHO **Treatment:** multiple stages 1. **Norwood procedure:** connection of main pulmonary artery to aorta to create new aorta, construction of modified Blalock-Taussig (systemic to pulm artery) OR Sano (RV to pulmonary artery) shunt to provide pulmonary flow, creation of large ASD, and coarctation repair 2. **bidirectional Glenn shunt:** connecting SVC to pulmonary artery - minimizes cyanosis and reduces volume load on RV 3. **modified Fontan procedure:** relieves cyanosis by connecting IVC to pulmonary artery via tube graft

Answer 298

heart failure

Answer 299

* occurs when heart is unable to maintain sufficient CO to meet metabolic demands of the body * can be caused by congenital OR acquired (cardiomyopathies, dysrrhythmias, electrolyte disturbances) * often result of decreased LV systolic function, and associated with left atrial and pulmonary venous HTN and pulmonary venous congestion * same compensatory mechanisms activated when CO falss

Answer 300

* poor feeding and sucking, often leading to failure to thrive * dyspnea, tachypnea, diaphoresis may be accompanied by retractions, grunting, nasal flaring * common skin changes - mottling, pallor

Answer 301

* Physical exam: * low weight with normal length and head circumferences * failure to thrive results from incresed metabolic expenditure relative to caloric intake * ECG * Chest X-ray - to assess presence of cardiomegaly and signs of increased pulmonary circulation/pulmonary edema * ECHO

Answer 302

* aimed at decreasing cardiac workload and increasing efficiency of heart function * medical management * diuretics (Lasix) * agents that reduce afterload (like enalapril and beta blockers) * if end-stage HF: ventricular assist device (VAD) while awaiting cardiac transplantation

Answer 303

* disease processes/abnormalities that occur after birth * various causes: infection, genetic disorders, autoimmune processes in response to infection, environmental factors, autoimmune disease)

Answer 304

**Description:** acute, self-limiting systemic vasculitis that may result in cardiac sequelae without treatment * primarily in young children (80% cases \<5 y.o.); males affected more; peak incidence is winter and spring **Etiology:** unknown (possible immunologic response to infectious, toxic, or antigenic substance) **Pathophysiology:** progresses in stages * _Early/acute phase_: small capillaries, arterioles, and venules become inflamed, as does the heart * _Subacute phase_: inflammation spreads to larger vessels and aneurysms of coronary arteries may develop * _Convalescent stage_: medium-sized arteries begin degranulation and may cause coronary artery thickening with increased risk for thrombosis * after ^ stage, inflammation wanes with potential scarring of vessels, calcification, and stenosis **Clinical Manifestations:** progresses in three stages * _Acute phase:_ fever, conjunctivitis, oral changes (strawberry tongue), rash, erythema of palms and soles, lymphadenopathy, often irritable; myocarditis may develop * _Subacute phase:_ begins when fever ends and continues until clinical signs have resolved; most at risk for coronary artery aneurysm at this stage; desquamation of palms and soles, marked thrombocytosis * _Convalescent phase:_ marked elevation of ESR and CROP level, increased platelet count; arthritis and arthralgia - this phase continues until all lab values return to normal (6-8 weeks onset) * Atypical/incomplete KD - those who lack Dx criteria (\< 4 S/S) **Diagnosis:** 5 of 6 major findings * Fever for 5+ days (unresponsive to antibiotics) * Bilateral conjunctivitis without exudation * Erythema of oral mucosa (strawberry tongue) * Changes in the extremities, such as peripheral edema and erythema with desquamation of palms and soles * Polymorphous (different stages/presentations) rash, often accentuated in perineal area * Cervical lymphadenopathy (one lymph node \> 1.5cm) **Treatment:** ASA and IV infusion of gamma globulins; most recover completely with regression of aneurysms * most common CV sequela: coronary thrombosis

Answer 305

**Description:** SBP and DBP \>95th percentile for age and gender on at least three occasions; etiology and presentation differ from adults * HTN classified into two categories: * **Primary/essential:** specific cause cannot be identified * **Secondary:** cause can be indentified **Pathophysiology:** in infants/children, HTN cause is almost always found * the younger the child with ++HTN, the more likely correctable cause * primary HTN: unclear but may be genetic predispositions with disturbances in sympathetic vascular smooth muscle tone, humoral agents, renal sodium excretion and CO **Clinical Manifestations:** commonly asymptomatic **Diagnosis/Evaluation:** BP measures obtained in right arm with arm supported at heart level; 3 separate measures needed * look at causes such as renal disease or Coartication of Aorta (COA) * CBC and various other routine evals for renal disease (urinalysis, electrolyte levels, etc.) * ECHO: to identify COA **Treatment:** * If COA founds: surgical correction/balloon angioplasty * If primary HTN: mod weight loss and exercise, diet, avoidance of smoking * potential med therapy (controversial): ACE inhibitors or ARBs