PATHO - Term Test II (Cardiovascular System) Flashcards
Functions of circulatory system
- delivery of oxygen, nutrients, hormones, immune system components, and other substances to body tissues
- removal of waste products of metabolism
The multifunctional tissue that needs to be healthy for normal vascular, immune, and hemostastic function is known as
vascular endothelium - a key component of the circulatory system
Wastes are removed via:
- lungs (gaseous wastes)
- kidneys/GI tract (other wastes)
List the blood vessel branches from arteries to veins
Arteries ⇒ arterioles ⇒ capillaries ⇒ venules ⇒ veins ⇒ heart
Which blood vessels allow the closest contact and exchange between blood and interstitial space (interstitium - where cells live)?
capillaries (
size of adult heart
200-350g; fist sized
Some of the plasma or liquid part of the blood passes through the walls of the capillaries into the interstitial space. This fluid is known as
lymph
Location of heart
Lies obliquely (diagonally) in the mediastinum (Area above diaphragm and between lungs)
Functionally, heart structures can be categorized as:
1) structural support of heart tissues and circulation of pulmonary and systemic blood through the heart
- heart wall and fibrous skeleton enclosing and supporting heart, dividing it into four chambers
- valves directing flow through chambers
- great vessels conducting blood to and from the heart
2) Maintenance of heart cells/cardiac metabolism
- vessels of coronary circulation
- heart’s lymphatic vessels
3) Stimulation and control of heart action
- nerves and specialized muscle cells that direct rhythmic contraction and relaxation of the heart muscles → properls blood through pulmonary and systemic circulatory systems
The layers of the heart are (outer to inner layer).
What is the heart enclosed in?
Three layers (outer to inner): epicardium, myocardium, endocardium
all enclosed in pericardium/pericardial sac
Pericardium
- double walled membrane sac
- two layers: parietal and visceral pericardium separated by pericardial cavity with pericardial fluid within (~20mL)
Function of pericardium
1) prevents displacement of heart during gravitational acceleration/deceleration
2) serves as physical barrier to protect heart against infection and inflammation coming from lungs/pleural space
3) contains pain receptors and mechanoreceptors that can cause reflex changes in BP and HR
Pericardial fluid
- fluid within pericardial cavity (~20mL) that is secreted by cells of mesothelial layer of pericardium
- lubricates membranes that line the pericardial cavity - allows them to slide smoothly over each other with minimal friction as the heart beats
- amount and character of pericardial fluid are altered if pericardium is inflamed
Trabecular carneeae
tubular projections of myocardial muscle that crisscross and project from the inner walls of the heart ventricles; covered by endocardium
Epicardium
outermost layer of the heart wall - has a smooth layer to minimize frction between heart wall and pericardial sac
myocardium
The thickest layer of the heart wall - made of cardiac muscle and is anchored to the heart’s fibrous skeleton
Cardiomyocytes
heart muscle cells - provide contractile force needed for blood to flow through heart and into pulmonary and systemic circulations
0.5-1% of these are replaced annually (so over a lifetime, ~half of these muscle cells are replaced)
Endocardium
- internal lining of myocardium - made of connective tissue and squamous cells
- continuous with endothelium that lines arteries, veins, and capillaries of the body to create closed circulatory system
4 possible approaches to myocardial regeneration after loss of muscle cells secondary to an MI
1) accelerating rate of heart cell division
2) inserting new cells into the heart
3) stimulating heart muscle precursor cells already in the heart
4) reprogramming other cells so they become cardiomyocyte precursor cells
Low-pressure system pumping blood through the lungs
R heart
high pressure system pumping blood to the rest of the body
L heart
Superior vena cava returns deoxygenated blood from
head and arms
Inferior vena cava returns deoxygenated blood from
trunk and legs
Function of atria
- storage units and channels for blood that is emptied into ventricles
- low pressure so thin walls
Function of ventricles
- contract to push blood through pulmonary and systemic vessels
- high pressure and thicker walls
Mean pulmonary artery pressure (force that the RV must overcome)
15mmHg
MAP for LV must pump against
~92mmHg (that’s why LV is 3x thicker than RV)
Calculate Mean Arterial Pressure (MAP) and identify the normal range
MAP = DBP + 1/3(SBP - DBP)
ex. someone with 120/80 BP
MAP = 80 + 1/3(120-80) = 93
Normal range: 70-110 mmHg
Shape of RV and what does this shape allow for?
crescent/triangle - enables a bellow-like action that efficiently ejects large volume through pulmonary SL valve into low pressure pulmonary system
Shape of LV and what does this shape allow for?
Bullet-shaped - allows generation of enough pressure to eject blood through relatively large aortic SL valve into high pressure systemic circulation
Each chamber in the heart can hold ~ ___mL of blood and since there are 4 chambers, the heart can hold ~ ____ mL of blood
70; 280
Function of septal membrane (i.e. interatrial and interventricular septum)
to separate R and L sides and prevent blood from crossing between the two circulatory systems
Foramen ovale
- 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
Function of fibrous connective tissue in the heart
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)
When ventricles are relaxed, __________valves open to allow blood to flow from relatively higher pressure in atria to lower pressure in ventricles.
atrioventricular (AV)
When do semilunar valves open?
When do they close?
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)
Structure of AV valves (and supporting structures)
- 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
Both pulmonic and aortic semilunar valves have ________ cusps that arise from fibrous skeleton.
1) three cup-shaped
2) two cup-shaped
3) four cup-shaped
1) three cup-shaped
R heart receives venous blood from systemic circulation via which blood vessels?
superior and inferior VC
Blood leaving the R ventricle enters pulmonary circulation through _____________. Where does this blood go?
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
____________ carry oxygenated blood from the lungs to the left side of the heart. How many blood vessels do this?
Four pulmonary veins - two from the right lung and two from the left
Each ventricular contraction and relaxation that follows it constitutes one _________.
Cardiac cycle
Diastole vs Systole
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
What are the 5 phases of cardiac cycle?
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
Normal Intracardiac pressures of:
1) RA
2) RV - Systolic
3) RV - end diastolic
4) LA
5) LV - systolic
6) LV - end diastolic
Where do the coronary arteries originate from?
Where do they receive blood from?
Originate at: upper edge of aortic semilunar valve cusps
Receive blood: through coronary ostia (openings in aorta)
The cardiac veins empty in (right atrium/left atrium) through another ostium, the opening of a large vein called ___________.
right atrium
coronary sinus
Major coronary arteries
RCA and LCA
How do coronary arteries differ between women and men? What contributes to this difference?
Coronary arteries are smaller in women than in men because women’s hearts weigh proportionally less than men’s hearts
Left Coronary Artery (LCA) - describe origin, structure/branches
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
Left Anterior Descending Artery (or Anterior Interventricular Artery) - describe structure and function
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
Circumflex Artery - describe structure and function
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
Right Coronary Artery - describe origin, structure/branches, and function
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)
Collateral Arteries - what are they and how are they formed
- 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
What is the benefit of having collateral arteries?
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
Coronary capillaries
- 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
Outline blood flow/pathway (i.e. where it flows into) after passing through capillary network in the heart.
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)
Describe the role of lymphatic vessels in the heart,
- 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
SA node - describe its location in the heart, innervation, discharge rate, and its effect
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)
AV node - location, innervation, function/effect
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
Conducting fibers from the AV node converge to form the __________
bundle of His (atrioventricular bundle) within posterior border of the interventricular septum
Right bundle branch (RBB)
- 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
Left Bundle Branch (LBB) - describe its branches
- 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
Purkinje fibers
- 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
Electrical activation of muscle cells is known as ___________, cause by the movement of ions across cardac cell membrane
Deactivation is known as __________.
depolarization
repolarization
Resting membrane potential for:
a) myocardial cells
b) SA node
c) AV node
a) -80 to -90 mV
b) -50 to -60 mV
c) -60 to -70 mV
Threshold (in the context of depolarization)
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
If the resting membrane potential becomes more negative because of a decrease in extracellular potassium concentration (hypokalemia), it is termed____________.
hyperpolarization
Refractory period (Absolute and Relative)
- 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
What do the following represent?
P wave
PR interval
QRS complex
ST interval
QT interval
T wave
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
Automaticity
- 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)
How is the heart able to beat in a heart transplant even with no innervation?
- Automatic cells of the cardiac conduction system can stimulate the heart to beat even when it is transplanted and thus has no innervation
Rhythmicity
- 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
ANS influences on the heart
- HR: the rate of impulse generation (firing), depolarization, and repolarization of myocardium
- contractility: strength of atria/ventricle contraction
True or false. Sympathetic and parasympathetic nerve fibers innervate all parts of the atria, ventricles, SA and AV nodes.
True
Sympathetic nervous activity on the heart
- 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
Parasympathetic nervous activity on the heart
- affects heart through vagus nerve which releases acetylcholine
- causes decreased HR and slows conduction through AV node
Structure of cardiomyocytes
- 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
Which of the following functions do cardiac muscles uniquely have due to its structural difference compared to skeletal muscle?
a) transmit action potentials quickly from cell to cell
b) maintain high levels of energy synthesis
c) gain access to more ions (particularly sodium and potassium, in extracellular environment)
d) all of the above are functions of cardiac muscle
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
Describe actin, myosin, and troponin-tropomyosin complex
- 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)
Troponin-Tropomyosin complex
- 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)
Titin
- 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
If myocardium is underperfused because of CAD leading to insufficient ATP production, what mechanisms kick in?
anaerobic metabolism
(typically ATP is synthesized in mitochondria mainly from glucose, fatty acids, and lactate)
Myocardial oxygen consumption (MVO2)
What is it, how is it determined, and what increases/decreases it?
- 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
Approximately _____% of oxygen is used immediately by cardiac muscle once coronary arteries deliver O2 to the myocardium
70-75% (little O2 left in reserve)
If the heart needs more oxygen, would it extract more oxygen from the blood or increase coronary blood flow (or both)?
- 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
Myocardial contractility
Define term, and what is happening at a molecular level.
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
Excitation-contraction coupling
Define and state how it is regulated/activated.
- 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
What are the two types of calcium channels in cardiac tissues?
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
How does the calcium-troponin complex interaction facilitates the contractin process in the heart?
- 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
At the molecular level, what is happening during myocardial relaxation?
If relaxation of myocardium is impaired, what would likely happen?
- 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
Normal cardiac output
~5L/min
(based on resting HR of 70 BPM and avg stroke volume of 70mL)
Ejection fraction
Definition, formula, normal values for men and women, and what causes it to increase/decrease.
- 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
Cardiac output influenced by what factors?
1) preload
2) afterload
3) myocardial contractility
4) HR
*the first three affect stroke volume
How does cardiovascular function change in the elderly in the following determinants, when at rest and during exercise?
a) Cardiac output
b) HR
c) Stroke volume
d) Ejection fraction
e) afterload
f) EDV
g) ESV (end-systolic volume)
h) Contraction
i) Myocardial wall stifness
j) Max Oxygen consumption
k) plasma catecholamines
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
Preload
- 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)
Laplace law
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.
Frank-Starling law of the heart
- 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)
Determine if SV increases or decreases in the following physiologic changes
a) increased preload (within physiologic range of muscle stretching)
b) excessive ventricular filling and preload (stretching heart beyond optimal length)
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)
Afterload
- 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
Systemic vascular resistance (SVR)
- 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
Stroke Volume
volume of blood ejected per beat during systole
Force of contraction (myocardial contractility) which influences stroke volume is determined by three major factors, which are:
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
An athlete would have (higher/lower) resting heart rate, (higher/lower) stroke volume, and (higher/lower) peripheral resistance.
a) lower HR
b) higher SV
c) lower peripheral resistance
What are the 5 things that control heart rate?
1) CNS
2) ANS
3) neural reflexes
4) atrial receptors
5) hormones
Where is the cardiovascular vasomotor control center located and what is its function?
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
Where are baroreceptors located and what is their function?
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
Where are the atrial receptors located and what is their function?
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
Bainbridge reflex
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)
Discuss how hormones/biochemicals influence heart rate
- 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
Peripheral vascular system
describes the part of the systemic cirulation that supplies the skin and extremities, particularly legs and feet
What are the three layers of the blood vessels?
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
Cells of larger vessel walls are nourished by _____________ which are small vessels located in tunica externa.
vasa vasorum
Artery
- 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
Elastic arteries - Structure and Function
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
Muscular arteries - Structure and Function
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
Arterioles - Structure and Function
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
The capillary network is composed of connect channels called ___________ and ___________. Describe their structures.
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)
Precapillary sphincter - Structure and Function
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
How does the structure of capillaries allow for rapid exchange of molecules?
What sorts of molecules can pass through capillaries and by what methods do said molecules pass through?
- 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
Size of capillaries
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
All tissues depend on a blood supply and the blood supply depends on ___________ which form the lining of the blood vessel.
endothelial cells
Function/role(s) of endothelium
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
Veins - Structure and Function
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
Muscle pump mechanism (venous return)
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
Blood flow - Definition and factors that influence blood flow
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
Pressure
- 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)
Resistance
- 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)
Poiseuille law
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
Poiseuille law - Factors that Increase Resistance
remember formula for Poisueille’s law: R = 8ηℓ/(πr4 )
- Viscosity: polycythemia, dehydration
- Length: increased body weight/height
- Radius (r4): Vasoconstriction (increase in SNS, decrease in vessel diameter)
Poiseuille law - Factors that decrease resistance
remember formula for Poisueille’s law: R = 8ηℓ/(πr4 )
- Viscosity: anemia
- Length: decreased body weight/height
- Radius (r4): Vasdodilation (decrease in SNS, increase in vessel diameter)
Total resistance
- 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
Blood velocity/speed
- 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
Laminar vs turbulent flow
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)
Arterial blood pressure is determined by what factors?
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
Reflex control of total cardiac output and peripheral resistance includes inputs? How are they regulated?
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
How do vasopressin and aldosterone affect BP?
- 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)
Lympathic system
- 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
Varicose veins
What is it, causes, pathophysiology, risk factors, treatment
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
Chronic Venous Insufficiency (CVI)
What is it, Causes, Pathophysiology, Symptoms, Treatment
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
Hypertension - Definition, prevalence, risk
- 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)
Primary HTN - Pathophysiology
- 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
Characterization and complications of myocardial hypertrophy secondary to complicated hypertension
- 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
Aneurysm
Description, Types, Causes/Pathophysiology, Clinical Manifestations, Diagnosis, Tx
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
Thromboangiitis Obliterans (Buerger Disease)
Description, Risk factor(s), Pathophysiology, Clinical Manifestations, Diagnosis, Tx
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
Atherosclerosis
Description, Risk Factors, Pathophysiology, Clinical Manifestations, Diagnosis, Tx
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)
Myocardial Ischemia
Pathophsyiology, Clinical Manifestations, Diagnosis and Treatment
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)
Acute Coronary Syndromes
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
How do atherosclerotic plaques become unstable/rupture and lead to ACS?
- 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
Myocardial Infarction (MI)
Description and Types
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
-
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
What are the three risk factors for sudden cardiac death?
1) ischemia
2) LV dysfunction
3) electrical instability
Diagnosis/Evaluation of MI
- 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
Cardiomyopathies
- 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
Dilated cardiomyopathy
- 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
Hypertrophic cardiomyopathy
- 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)
Heart failure with reduced ejection fraction (HFrEF)
Definition and Pathophysiology
- 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
Right Heart Failure
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)
High-Output Failure
Description, causes, pathophysiology
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
The final common pathway in shock of any type is:
impairment of cellular metabolism
Cardiogenic shock
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
Hypovolemic shock
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
Neurogenic Shock
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
Anaphylactic Shock
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!
Septic Shock
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
Multiple Organ Dysfunction Syndrome (MODS)
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
Coarctation of the Aorta (COA)
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)
Aortic Stenosis (AS)
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
Pulmonic Stenosis (PS)
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
Patent Ductus Arteriosus (PDA)
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
Atrioventricular Canal (AVC) Defect
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
Tetralogy of Fallot (TOF)
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)
Tricuspid Atresia
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
Transposition of the Great Arteries (TGA)
or
Transposition of the Great Vessels (TGV)
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
Total Anomalous Pulmonary Venous Connection (TAPVC)
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
Truncus Arteriosus (TA)
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:
- Type I: Single pulmonary trunk arises near base of truncus and divides into left and right pulmonary arteries
- Type II: L and R pulmonary arteries arise separately from posterior aspect of truncus
- 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
Hypoplastic Left Heart Syndrome (HLHS)
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
- 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
- bidirectional Glenn shunt: connecting SVC to pulmonary artery - minimizes cyanosis and reduces volume load on RV
- modified Fontan procedure: relieves cyanosis by connecting IVC to pulmonary artery via tube graft
