Exam Review Week 1 Flashcards
What is myocardial ischemia?
condition in which myocardial oxygen supply does not meet demands and there is myocardial hypoxia
What is angina?
chest pain, typically as a result of myocardial ischemia
What is myocardial infarction?
irreversible necrosis of heart muscle – Heart Attack; occurs if you have enough ischemia
What are cardiomyopathies?
diseases of the muscle
What is a dilated cardiomyopathy?
disease of the muscle caused by infections, toxins, unknown
What is hypertrophic cardiomyopathy?
familial, genetic disease of the muscle
What is restrictive cardiomyopathy?
disease of the muscle caused by infiltrative processes
What are the parts of the cardiac cycle on those square-shaped volume and pressure plots?
bottom of square = filling; right side = isovolumic contraction; top = ejection; left side = isovolumic relaxation
What are some examples of valvular heart disease?
Aortic valve disease Aortic stenosis Aortic regurgitation Mitral valve disease Mitral regurgitation Mitral stenosis Tricuspid and Pulmonic valve disease Prosthetic Heart Valves Endocarditis
What is the typical cause of coronary artery disease?
atherosclerosis
What arrhythmias cause the heart to go too slowly?
heart blocks (1st, 2nd, and 3rd degree)
What arrhythmias cause the heart to go too quickly?
Supraventricular arrhythmias (SVT, atrial fibrillation, atrial
flutter); Ventricular arrhythmias (ventricular tachycardia,
ventricular flutter)
What is pericarditis?
inflammation of the pericardium (multiple causes, including infectious, trauma, radiation)
What is Pericardial Tamponade?
a form of cardiogenic shock
What is heart failure?
Heart failure is the final and most severe manifestation of nearly every form of cardiac disease. Heart failure is present when the heart is unable to pump blood forward at a sufficient rate to the meet metabolic demands of the body or is able to do so only if the cardiac filling pressures are abnormally high or both.
What are clinical sequellae of atherosclerosis?
stroke (embolic or thrombotic), coronary artery disease, renal artery disease, aneurysms, peripheral artery disease
What is prevalence?
Prevalence is an estimate of how many people have a disease at a given point in time
An estimated 80,700,00 American adults (1 in 3) have 1 or more types of cardiovascular disease.
What is incidence?
Incidence refers to the number of new cases of a disease that develop in a population per unit of time.
The average annual rate of first CV events rises from 3/1000 men at 35-44years of age to 74/1000 men at 85-94 years of age. For women, comparable rates occur 10 years later in life.
What are modifiable risk factors for cardiovascular disease?
Dyslipidemia Tobacco smoking High blood pressure Diabetes mellitus/metabolic syndrome Lack of physical activity Obesity
What are non-modifiable risk factors for cardiovascular disease?
Advanced age
Male gender
Heredity
What is normal BP? Pre-hypertension? Hypertension?
Normal: less than 120/80mmHg;
Prehypertension: 120-139 or 80-89
Hypertension: more than 139 systolic or 89 diastolic
What are hypertension risk factors?
family history; Black; prehypertension; increasing age; obesity; high sodium-low potassium intake; excessive alcohol intake; low socioeconomic status; sleep apnea; some illicit drugs or OTCs
What is the DASH diet?
Emphasizes vegetables, fruits. Fat-free or low-fat dairy products; Includes whole grains, fish, poultry, beans, seeds, nuts, and vegetable oils; Limits sodium, sweets, sugary beverages, and red meats
What are lymphatics?
Drain clear fluid (lymph) from tissue spaces (they are more permeable than capillaries). Chyle from GI tract is white with lipid. Endothelium: fenestrated and non-fenestrated. Basement membrane: continuous or non-continuous. Have valves as do veins. Large lymphatics have muscle in wall.
What are the parts of an artery?
intima, media, adventitia; also contains endothelium, internal elastic lamina, external elastic lamina
What is epithelium?
epithelium covers the body surface or lines ducts in solid organs
What is endothelium?
endothelium lines blood vessels & lymphatics
What is contained in the intima?
Endothelium (Continuous (have tight junctions), Fenestrated (intestine, endocrine organs, glomeruli)) Basal Lamina Myointimal cells (smooth muscle, produce collagen, phagocytic ability)
What are the types of capillary endothelium?
- Continuous (e.g. in muscle; tight junctions, pavement-like);
- Fenestrated (fenestrations within endothelial cells; e.g. endocrine glands)
- Sinusoidal (gaps between endothelial cells) (e.g. liver)
What are the functions of endothelium?
1.Barrier – tight junctions
2.Filtering and transport – fenestrated endothelium, pinocytotic vesicles, active transport via proteins (blood-brain barrier)
3.Secretion – vasodilation ( prostacyclin, nitric oxide) & vasoconstriction (angiotensin-converting enzyme (ACE), endothelin)
4.Cell growth – increase (PDGF) or decrease (heparin, TGF-beta)
5.Clotting – inhibit (prostacyclin and NO inhibit platelet aggregation, tissue plasminogen activator regulates fibrinolysis, thrombomodulin) or promote (tissue factor, platelet activating factor, von Willebrand factor)
5.Lipoprotein metabolism: oxidation of low density lipoproteins (LDL) and VLDL
6.Produce extracellular matrix – Type IV collagen, laminin, proteoglycans
7. Immunologic
Activated by cytokines to produce adhesion molecules (selectins, integrins, CD markers).
Which cardiac imaging modalities use radiation? Which don’t?
Radiation: CXR, cardiac CT, nuclear, cardiac catherization, PET; no radiation: echocardiography, cardiac MRI
What is a chest X-ray? How does it work?
Utilizes ionizing radiation to penetrate the body and takes advantage of the fact that penetration is inversely related to tissue density. The lung, an air-filled tissue absorbs few x-rays and appears black. The heart has a density similar to blood. Heart borders adjacent to the lung are clearly depicted because of the different densities.
What can you assess with a chest x-ray?
- cardiac and mediastinal contours
2. pulmonary vascular markings
What are the clinical uses of a chest x-ray?
detect chamber enlargement; detect vessel enlargement; detect pulmonary vascular signs of heart failure; detect shunts (abnormal communication between
cardiac chambers)
What are advantages to chest x-ray? Disadvantages?
Advantages: can be portable;
Disadvantages: radiation, a projection technique where there is superimposition of multiple structures
What is cardiac catheterization? How does it work?
- Intravascular catheters are inserted to measure cardiac pressures and blood flow; 2. Contrast agents can be injected and x-ray can produce a cineangiogram
What can you assess with cardiac catheterization?
1.Pressures in the heart chambers; 2.Measurement of blood flow (cardiac output); 3.Calculation of vascular resistance; 4.Ventricular function, valvular regurgitation, and coronary anatomy
What are clinical uses of cardiac catheterization?
Identify coronary anatomy and severity of stenoses; Visualize ventricular contractile function; Assess valvular regurgitation; Measure intracardiac pressures
What are advantages to cardiac catheterization? Disadvantage?
Advantages:
- Direct measurement of cardiac pressures
- Identify coronary anatomy and severity of stenosis
Disadvantages:
- invasive (must enter artery and/or vein)
- involves radiation
- Contrast can be allergic and damage kidneys, especially in patients with renal dysfunction or diabetes
What is the LAD and what does it supply?
left anterior descending coronary artery;
supplies the anterior two-thirds of the interventricular septum
supplies apical portion of the anterolateral papillary muscle
supplies the anterior surface of the left ventricle
supplies a portion of the anterior RV wall
What is the LCX and what does it supply?
left circumflex coronary artery:
supplies the lateral and posterior walls of the left ventricle
supplies the anterolateral papillary muscle
What is the RCA and what does it supply?
right coronary artery:
supplies blood to the right ventricle
supplies blood to the inferior and posterior walls of the left ventricle
supplies blood to the posterior one-third of the interventricular septum
supplies AV nodal artery (85% of the population)
supplies the SA nodal artery (70% of the population)t
supplies the posteromedial papillary muscle
What is computed tomography? How does it work?
CT!
uses thin x-ray beams to obtain axial plane images. An x-ray tube is programmed to rotate around the body and the generated beams are partially absorbed by body tissues. The remaining beams emerge and are captured by electronic detectors and a computerized image is composed. Intravenous contrast is usually required to distinguish intravascular contents from neighboring soft tissue.
What can you assess with CT?
great vessels
pericardium
myocardial structures
coronary arteries
What are clinical uses of CT?
Diagnose diseases of the great vessels (for example, pulmonary embolism, aortic dissection); Assess pericardial disease/effusion; Detect coronary artery calcification and
stenoses
What are advantages of CT? Disadvantages?
Advantages: rapid, relatively inexpensive, and less invasive than conventional angiography
Disadvantages: significant radiation exposure, not as sensitive as conventional angiography
What is magnetic resonance imaging? How does it work?
MRI!
uses a powerful magnetic field to align the spin or protons followed by a brief radiofrequency pulse to perturb the steady state of the protons. A signal is generated when the protons return toward their steady state that can be used to generate images.
What can you assess with MRI?
- Best technique for differentiating tissue contrasts (blood, fluid, fat, myocardium)
- Ventricular mass and volume
- Diseases of the aorta (aneurysm, dissection)
- Neoplastic disease
- Congenital heart disease
- With gadolimium-based (noniodinated) contrast, can distinguish viable from non-viable myocardial segments
What are clinical uses of MRI?
Assess myocardial structure and function, accurate assessment of ejection fraction, may be best way to assess the function of the right ventricle; Assessment of congenital heart disease; Assess cardiac tumors; Assess aortic and pericardial disease; Assess coronary arteries including coronary artery anomalies
What are advantages of MRI? Disadvantages?
Advantages: involves no radiation, excellent at differentiating tissue contrasts (blood, fluid, fat, myocardium)
Disadvantages: specialized equipment requiring specialized facilities, patient may feel claustrophobic, patients with pacemakers, other metal devices excluded
What is Single-Photon Emission Computed Tomography (SPECT) Imaging? How does it work?
Uses a gamma camera to non-invasively image the cardiac distribution of intravenously injected radiotracers. As the unstable radiotracer decays, gamma rays are emitted. The emitted gamma rays are collected as the gamma camera rotates around the patient. This data is then used to create an image of the heart.
What can you assess with SPECT?
- Myocardial perfusion
- Left ventricular systolic function
- Left ventricular volumes
- Myocardial viability
What is Positron Emission Tomography (PET) Imaging? How does it work?
Uses multiple radiation detectors configured in a ringed gantry to register the coincident events of the annihilation reaction of positrons and electrons after positrons are emitted from positron-emitting radiopharmaceuticals. The recorded events are then used to reconstruct an image of the heart.
What can you assess with PET?
- Myocardial perfusion
- Absolute coronary blood flow
- LV systolic function
- Myocardial viability
- Myocardial metabolism
What are the clinical uses of PET?
Distinguish viable myocardium from scar tissue; fEvaluate contractile function
What are advantages of PET? Disadvantages?
Advantages: High spatial resolution images, No artifacts from overlying tissue, Quantitative analysis performed, Relatively fast tests because half lives of tracers are very short
Disadvantages: Limited, though increasing availability of PET scanners, Limited availability of radiotracers, if no cyclotron, Can only perform pharmacologic stress, Radiation exposure
What is echocardiography? How does it work?
Uses ultrasound (high-frequency sound waves) which travels through tissue and is able to image structures because of the different acoustic impedances of adjacent tissues.
What are clinical uses of echocardiography?
- Assess ventricular function
- Identify valve abnormalities and vegetations
- Identify myocardial infarction and complications
- Identify congenital abnormalities
- Visualize intracardiac thrombus
- Evaluate prosthetic valves
- Diagnose aortic dissection
What are advantages of echocardiography? Disadvantages?
Advantages: no radiation, portable, tomographic imaging
can estimate intracardiac pressures non-invasively;
Disadvantages: technical limitations in obesity, lung disease although these limitations can be overcome by using transesophageal echo (but more invasive)
What is excitation-contraction coupling?
process from electrical excitation of the myocyte to contraction of the heart or skeletal muscle
What is the direct activator of the myofilaments?
calcium
What influences muscle tension?
Muscle length - active tension depends on the degree of overlap between thick and thin filaments
What does abrupt onset of skeletal muscle contraction depend upon?
Abrupt onset of active state in large, rapidly contracting skeletal muscles does not depend upon Ca2+ from extracellular space, but upon the release of Ca2+ from intracellular stores; Allows for activator to reach binding sites by a shortened diffusion path in skeletal muscle.
What does the onset of cardiac muscle contraction depend upon?
depends upon Ca2+ from extracellular space to initiate contraction
What is the structure of a skeletal muscle?
Muscle made up of muscle fascicles surround by epimysium; each fascicle contains muscle fibers surrounded by perimysium; each muscle fiber contains myofibrils surrounded by endomysium; each myofibril contains myofilaments, which are organized in sarcomeres (actin and myosin)
How many nuclei are in skeletal muscle? Cardiac muscle?
Unlike skeletal myofibers, myocytes contain only 1-2 centrally located nuclei.
What are T-tubules?
invaginations of the sarcolemmal membrane that surrounds the cell; are extracellular space– allow Ca2+ trigger to be delivered deep within the myocyte. Increase surface area of sarcolemma. Allow for rapid transmission of excitatory electrical impulses that initiate contraction
What is the intercalated disk?
Specialized region of the membrane; Seen on light microscopy as darkly staining traverse lines that cross chains of cardiac cells at irregular intervals; Represent gap junction complexes at interface of adjacent cardiac fibers; Establish structural and electrical continuity between myocardial cells
What is sarcoplasmic reticulum?
Sarcoplasmic reticulum (SR) extensive intracellular tubular membrane network. SR abuts T tubules at right angles in lateral sacs (terminal cisternae). Intracellular Ca2+ stores.
Where do you find mitochondria in the muscle?
Abundant concentration of mitochondria—located between individual myofibrils and constitute about 35% of cell volume
What is the variation in Z-Z distance during cardiac cycle?
Z-Z distance varies during cardiac cycle: during ventricular filling- 2.2 mm During contraction, 1.5 mm
Where does atherosclerosis proliferate?
The intima
How are blood vessels innervated?
Adrenergic – vasoconstriction
Cholinergic – vasodilation
Afferent- pressure receptors, chemoreceptors
Carotid bodies connect by the glossopharyngeal nerve to the brain stem.
What do High endothelial venules do?
High endothelial venules facilitate lymphocyte adhesion and migration. HEV have receptors (GlyCAM-1, ICAM-1, CD34) for ligands on naïve lymphocytes (CCR7, L-selectin, LFA-1).
What is seen in atherosclerosis (pathology)?
Fibrous cap, stable plaques, calcification, lipid core with “cholesterol clefts”
What is seen in severe atherosclerosis (pathology)?
‘complicated’ plaques with ulceration and thrombus
What is the epicardium?
Secretes fluid to allow heart to move in epicardial sac; Mesothelium (M) lines the visceral and parietal pericardium; found on the surface of the heart
What is B-type natriuretic protein (BNP)?
Increases water, Na, K excretion by kidney.
Inhibits renin secretion by kidney.
Inhibits aldosterone secretion by adrenals.
What do myocytes of the myocardium do?
Contraction.
Secretion: atrial cells secrete B-type natriuretic protein (BNP) when stretched.
What is the sinoatrial (SA) node?
the ‘pacemaker’; at junction of SVC with atrium (not visible grossly – 1 cm x 0.1 cm); Fibers 3-4 microns in diameter and with few myofibrils and desmosomes rather than intercalated disks.; Embedded in connective tissue with a central nodal artery.
What is the Atrioventricular (AV) Node?
Adjacent to opening of coronary sinus above tricuspid valve ring. Small fibers in connective tissue.
What is the Bundle of His?
Left bundle branch - a diffuse fan of fibers.
Right bundle branch - more distinct
Connect with Purkinje fibers in ventricles.
What are Purkinje fibers?
Myocytes with abundant glycogen and few myofibrils; found in the subendocardium
What is spongiosa?
a looser connective tissue layer in the valves
What is fibrosa?
denser connective tissue in the valves
Where is the primary mutation in most familial hypertrophic cardiomyopathy?
Beta-myosin heavy chain is site of mutation in 35%
What are the parts of the heart muscle?
epicardium, myocardium, endocardium
What is endocardium?
Faces the chamber
What is the valve composed of?
Mostly collagen
What is the difference between epithelium and endothelium?
endothelium vs epithelium - endothelium line blood vessels (derives from mesoderm) - is flat but not squamous cell
What is the A band?
region of sarcomere occupied by thick filaments into which thin filaments extend from either side. When viewed through crossed polarizing lenses, the more darkly staining bands rotate the polarized light (birefringent or anisotropic). This ability indicates that the A-bands contain a highly ordered parallel array of macromolecules.
What is the I band?
more lightly staining; less birefringent and isotropic. I-band is the region of the sarcomere occupied only by thin filaments, which extend to the center of the sarcomere Each I-band is bisected a narrow, darkly staining Z-line.
What is the H zone?
contains thick filaments- no overlap with thin filaments.
What is the Z disk?
The Z-disk is a structural lattice composed of ends of actin, titin and nebulin, cross-linked by alpha-actinin. Serves as the anchoring plane of thin actin filaments and titin from opposing sarcomere halves.
What is titin?
keeps thick filament centered in sarcomere during activation; functions as a molecular spring responsible for the development of a retractive force during stretch of nonactivated (relaxed) muscle
What does nebulin do?
helps align thin filaments in sarcomere
What is a costamere?
protein complex consisting of cytoskeleton, transmembrane glycoproteins and extracellular matrix at level of Z bands-involved in transferring tension from contractile elements to connective tissue- may serve as mechano-sensor for signal transduction.
How does muscle contraction affect the different bands?
As muscle shortens, lengths of both thick and thin filaments remain constant. As sarcomere length decreases, thin filaments are pulled into thick filament lattice of A band; causes I-band to narrow, whereas A band remains constant. Thin filaments pulled towards center by motion of cross-bridges that project from thick filaments to thin filaments
What is myosin?
Myosin is the major protein of thick filaments; rigid tails are woven in the backbone of the filament; enzymatically active heads project as cross-bridges. Tail is coiled coil, made up of 2 a-helical peptide chains wound around each other. In addition to 2 heavy chains, cardiac myosin contains 2 pairs of light chains; associated with hinge regions. Myosin heads have ATPase activity- hydrolysis of ATP by myosin head is the energy source to drive muscle contraction.
What is the structure of actin/thin filaments?
Thin filaments are composed of actin, troponin and tropomyosin.
Monomeric form: G-actin (globular; present under low salt)
Polymeric form: F-actin (fibrous); basic structural unit of the thin filament; troponin and tropomyosin bind to F-actin.
Structure: each strand is a chain of actin monomers; essentially, 2 strings of beads wound around each other. Each 1/2 turn of the F-actin filament contains 7 pairs of actin monomers.
What is tropomyosin?
relatively inflexible elongated molecule that regulates the interactions between actin and myosin. One molecule of tropomyosin lies in each of the 2 grooves that run longitudinally between the 2 strands of actin. Adds structural rigidity and participates in regulation of contraction.
What is troponin?
made up of 3 proteins;
Troponin I, in concert with tropomyosin regulates interactions between actin and myosin- inhibits interaction between actin and myosin
Troponin T, binds troponin complex to tropomyosin.
Troponin C, contains Ca2+ binding sites. Binding of Ca2+ to troponin C causes a conformational change, shifting physical location of tropo-myosin and exposing the active sites of actin to interact with myosin
What affects myofilament calcium sensitivity?
Myofilament Ca2+ sensitivity is reduced by acidosis, elevated phosphate and Mg2+ concentrations (occur in ischemia). Also reduced by b-adrenergic activation, but enhanced by caffeine and certain inotropic drugs. Rapid kinetics of Ca2+ transient prevent myofilaments from equilibrating during normal twitch Thus, although contractile strength is indicative of underlying Ca2+ transient, there is a dynamic interplay between Ca2+ and myofilaments during E-C coupling.
What triggers the heart to contract?
Process is graded and depends upon Ca2+ and other factors. Membrane depolarization activates L type Ca2+ channel. Ca2+ enters cell through ICa, but also through Na+- Ca2+ exchanger Ca2+ influx triggers SR Ca2+ release through ryanodine receptors- known as Ca2+-induced Ca2+ release (CICR).
What is the Na-Ca2+ exchanger?
Reversible; can transport Ca2+ in or out of cell.
stoichiometry of 3 Na+ ions to 1 Ca2+ ion; produces ionic current (INa/Ca).
High intracellular Ca2+ favors Ca2+ efflux, whereas positive membrane potential and high intracellular Na+ favors Ca2+ influx.
Under physiologic conditions, NCX works mainly in the Ca2+ extrusion mode, driven by the Ca2+ transient. The positive membrane potential can limit Ca2+ extrusion.
The amount of Ca2+ influx can be increased greatly if intracellular Na+ is elevated (i.e. digitalis), if SR Ca2+ release and/or ICa is inhibited or if action potential duration is prolonged.
What happens at high SR Ca2+?
High load of SR Ca2+ in the SR directly increases the amount of Ca2+ available for release and greatly enhances the fraction of SR Ca that is released for a given ICa trigger.
High SR Ca2+ is the basis for after-contractions, transient inward current and delayed after-depolarizations that can trigger arrhythmias.
What happens at low SR Ca2+?
At low SR Ca content, ICa can fail to induce Ca2+ release from the SR- may help to reload SR; less inactivation of ICa and less Ca2+ extrusion through NCX.
SR Ca2+ content can be raised by increasing Ca2+ influx, decreasing Ca2+ efflux or enhancing Ca2+ uptake into SR.
What is SERCA?
SR Ca2+ ATPase, relaxes myofilaments
What is Phospholamban?
endogenous inhibitor of SERCA. Phosphorylation of phospholamban by PKA or CaMKII relieves inhibition, allowing faster twitch relaxation and decline of intracellular Ca2+. SERCA would then compete better with NCX, leading to enhanced Ca2+ content in SR.
What is the basic process of excitation-contraction coupling?
- Cardiac action potential initiated in myocardial cell membrane; spreads to interior via T tubules.
- Ca2+ entry induces Ca2+ induced Ca2+ release. Key: how much Ca2+ is stored and amount of inward Ca2+ through L-type Ca2+ channel.
- Ca2+ binds to troponin C, tropomyosin moved out of way, interaction between actin and myosin.
- Magnitude of tension proportional to intracellular [Ca2+].
- Relaxation: Ca2+ pumped back to SR and out of cell.
How does the sympathetic nervous system affect cardiac contractility?
Increased inotropy
Increased peak tension, increased rate of tension development and and lusitrophy (relaxation).
Faster relaxation means that contraction twitch is shorter, allowing more time for refilling.
PKA phosphorylates several proteins including Cav1.2, RyR, phospholamban, troponin I and myosin binding protein C. Increased Ca2+ release and uptake more than offsets the reduction in myofilament Ca2+ sensitivity (due to troponin I phosphorylation).
How does the parasympathetic nervous system affect cardiac contractility?
Opposes the effects of b-adrenergic stimulation– especially in atrial cells- not prominent in ventricle
Acetylcholine (ACh), released from parasympathetic nerve terminals binds to muscarinic receptor on cardiac cells. Coupled to inhibitory G protein, which inhibits adenylate cyclase activity and reduces cAMP formation.
ACh decreases inward Ca2+ current during AP plateau
Also activates specific types of K+ channels, which hyperpolarize membrane. In sinus node, serve to decrease heart rate. Together, decrease amount of Ca2+ entering atrial cells, decrease trigger Ca2+ and decrease amount of SR Ca2+ release.
How does heart rate affect contractility?
More action potentials per unit time and an increase in the total amount of trigger Ca2+ that enters the cell during the plateau phase of the action potential; Increased Ca2+ entry leads to increased SR Ca2+ load; Increased heart rate may be due to increased sympathetic tone, which further increases Ca2+ entry and load
